Glycoconjugate vaccines against antimicrobial resistant pathogens

Antimicrobial resistance (AMR) is responsible for the death of millions worldwide and stands as a major threat to our healthcare systems, which are heavily reliant on antibiotics to fight bacterial infections. The development of vaccines against the main pathogens involved is urgently required as prevention remains essential against the rise of AMR. A systematic research review was conducted on MEDLINE database focusing on the six AMR pathogens defined as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli), which are considered critical or high priority pathogens by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). The analysis was intersecated with the terms carbohydrate, glycoconjugate, bioconjugate, glyconanoparticle, and multiple presenting antigen system vaccines.Glycoconjugate vaccines have been successful in preventing meningitis and pneumoniae, and there are high expectations that they will play a key role in fighting AMR. We herein discuss the recent technological, preclinical, and clinical advances, as well as the challenges associated with the development of carbohydrate-based vaccines against leading AMR bacteria, with focus on the ESKAPE pathogens. The need of innovative clinical and regulatory approaches to tackle these targets is also highlighted.Horizon 2020(H2020)861194Bio-organic Synthesi

First results obtained using the CENBG nanobeam line: performances and applications

A high resolution focused beam line has been recently installed on the AIFIRA (“Applications Interdisciplinaires des Faisceaux d’Ions en Région Aquitaine”) facility at CENBG. This nanobeam line, based on a doublet–triplet configuration of Oxford Microbeam Ltd. OM-50™ quadrupoles, offers the opportunity to focus protons, deuterons and alpha particles in the MeV energy range to a sub-micrometer beam spot. The beam optics design has been studied in detail and optimized using detailed ray-tracing simulations and the full mechanical design of the beam line was reported in the Debrecen ICNMTA conference in 2008. During the last two years, the lenses have been carefully aligned and the target chamber has been fully equipped with particle and X-ray detectors, microscopes and precise positioning stages. The beam line is now operational and has been used for its firstapplications to ion beam analysis. Interestingly, this set-up turned out to be a very versatile tool for a wide range of applications. Indeed, even if it was not intended during the design phase, the ion optics configuration offers the opportunity to work either with a high current microbeam (using the triplet only) or with a lower current beam presenting a sub-micrometer resolution (using the doublet–triplet configuration). The performances of the CENBGnanobeam line are presented for both configurations. Quantitative data concerning the beam lateral resolutions at different beam currents are provided. Finally, the firstresults obtained for different types of application are shown, including nuclear reaction analysis at the micrometer scale and the firstresults on biological sample

Archean (3.33 Ga) microbe-sediment systems were diverse and flourished in a hydrothermal context

International audienceInteracting, diverse microbe-sediment systems exist in natural environments today but have not yet been recognized in the oldest records of life on Earth (older than 3.3 Ga) because of lack of distinctive biomarker molecules and patchy preservation of microbial paleocommunities. In an in-situ outcrop-to microbial-scale study, we have differentiated probable phototrophic, chemolithotrophic, and chemo-organotrophic fossil microbial signatures in a nearshore vol-canogenic sedimentary setting in 3.33 Ga rocks of the Josefsdal Chert, Barberton greenstone belt, South Africa, while demonstrating the importance of contemporaneous hydrothermal activity. Hydrothermal fluids, as a nutrient source, strongly controlled the development and distribution of the microbial communities and, as a silicifying agent, contributed to their rapid fossilization. We thus show that intricate microbe-sediment systems are deep-rooted in time and that at least some early life may indeed have been thermophilic. INTRODUCTION Microbial communities in natural environments exist as multispecies assemblages that interact directly with one another and with their surroundings, and thus can be viewed as distinctive systems (Nealson, 1997). For example, a wide diversity of organotrophic and lithotro-phic (chemotrophic) microorganisms has been described in present-day, carbon-rich hydrother-mally influenced basaltic sediments (Callac et al., 2013), similar to those described from early Earth. However, lack of specific biomarker preservation in very ancient rocks (Summons, 1993) and haphazard preservation of microbial communities in general (Campbell et al., 2001; Orange et al., 2009) make tracing such systems in fossilized form to the oldest records of life on Earth (early Archean, older than 3.3 Ga) very challenging. Nevertheless, phototrophic microbial communities in early to mid-Archean (ca. 3.5–3.2 Ga) strata of South Africa and Australia have been well documented (). On the other hand, no previous investigations have recognized and addressed the syngenetic diversity of Archean microbial paleocommunities—both phototrophs and che-motrophs —within their sedimentary habitats at the microbial scale and using in-situ methods. Here we describe a macroscopic to microscopic investigation of the sedimentary and geochemical settings of widespread, fossilized phototrophic and chemotrophic microorganisms in early to mid-Archean (3.33 Ga) coastal sediments from the Josefsdal Chert, Barberton greenstone belt, South Africa. We also emphasize the importance of contemporaneous hydrothermal activity both as a source of energy for biomass production and as the means of preserving the biosignatures

Changing potency by spontaneous fusion

Recent reports have suggested that mammalian stem cells residing in one tissue may have the capacity to produce differentiated cell types for other tissues and organs (1–9). Here we define a mechanism by which progenitor cells of the central nervous system can give rise to non-neural derivatives. Cells taken from mouse brain were co-cultured with pluripotent embryonic stem cells. Following selection for a transgenic marker carried only by the brain cells, undifferentiated stem cells are recovered in which the brain cell genome has undergone epigenetic reprogramming. However, these cells also carry a transgenic marker and chromosomes derived from the embryonic stem cells. Therefore the altered phenotype does not arise by direct conversion of brain to embryonic stem cell but rather through spontaneous generation of hybrid cells. The tetraploid hybrids exhibit full pluripotent character, including multilineage contribution to chimaeras. We propose that transdetermination consequent to cell fusion (10) could underlie many observations otherwise attributed to an intrinsic plasticity of tissue stem cells (9)

Correlation between Hydrogen distribution and Raman mapping in carbonaceous matter.

International audienc

Pigment darkening as case study of In-Air Plasma-Induced Luminescence

We introduce the use of an In-Air Plasma-Induced Luminescence (In-Air-PIL) spectroscopy as an alternative to classical chemical and crystallographic methods used in materials science. The In-Air-PIL is evaluated on a case study investigating the effect of light aging on the darkening of five pristine yellow pigments commonly used in artworks. We show that the darkening is not associated to changes in the chemical composition, but to a loss in crystallinity, indicating an amorphization process of the pigments induced and catalyzed by the light irradiation. This favors the interaction of the pigment molecules with oxygen and carbon adsorbed from the environment or solved in the binding agent, subsequently leading to the formation of oxalates and carbonates as observed in other works. We demonstrate that the In-Air-PIL results are in perfect agreement with more complex classical materials science analysis methods, making our plasma-driven method a potentially easier and faster technique

Two conifer GUX clades are responsible for distinct glucuronic acid patterns on xylan

Wood of coniferous trees (softwood), is a globally significant carbon sink and an important source of biomass. Despite that, little is known about the genetic basis of softwood cell wall biosynthesis. Branching of xylan, one of the main hemicelluloses in softwood secondary cell walls, with glucuronic acid (GlcA) is critical for biomass recalcitrance. Here, we investigate the decoration patterns of xylan by conifer GlucUronic acid substitution of Xylan (GUX) enzymes. Through molecular phylogenetics we identify two distinct conifer GUX clades. Using transcriptional profiling we show that the genes are preferentially expressed in secondary cell wall forming tissues. With in vitro and in planta assays we demonstrate that conifer GUX enzymes from both clades are active glucuronyltransferases. Conifer GUX enzymes from each clade have different specific activities. While members of clade one add evenly spaced GlcA branches, the members of clade two are also capable of glucuronidating two consecutive xyloses. Importantly, these types of xylan patterning are present in softwood. As xylan patterning might modulate xylan-cellulose and xylan-lignin interactions, our results further the understanding of softwood cell wall biosynthesis and provide breeding or genetic engineering targets that can be used to modify softwood properties

Recrystallization of amorphous ion implanted silicon carbide after thermal annealing

Single crystals of 6H-SiC were implanted at room temperature with 4-MeV Au ions to a fluence of 1015cm 2. Raman spectra showed that full amorphization was achieved. The recrystallization process was studied by micro-Raman spectrometry after isochronal thermal annealing between 700 and 1500 C. The spectra permitted the evolution upon annealing of Si-C bonds, and also of Si-Si and C-C bonds, to be followed. Amorphous phase relaxation takes place below 700 C; then recrystallization of the 6H polytype sets in at 700 C. At 900 C crystallites with different crystalline states are formed. Moreover, Raman spectra provide evidence of graphitic nanocluster formation at 1500 C