F-Fluorination of Nitroimidazolyl-Containing Sultone: A Direct Access to a Highly Hydrophilic Radiotracer for High-Performance Positron Emission Tomography Imaging of Hypoxia.

Hypoxia, characterized by nonphysiological levels of oxygen tension, is a key phenomenon common to the majority of malignant tumors with poor prognosis. Many efforts have been made to develop hypoxia imaging for diagnosis, staging, and monitoring of diseases, as well as for evaluating therapies. PET Imaging using F-fluoronitroimidazoles (i.

Impact of the environmental parameters on single cell protein production and composition by Cupriavidus necator.

Due to the rapid increase in the world's population, many developing countries are facing malnutrition problems, including famine and food insecurity. Particularly, the deficiency of protein sources becomes a serious problem for human and animal nutrition. In this context, Single Cell Proteins, could be exploited as an alternative source of unconventional proteins.

Autotrophic Production of the Sesquiterpene α-Humulene with in a Controlled Bioreactor.

is a facultative chemolithotrophic organism that grows under both heterotrophic and autotrophic conditions. It is becoming increasingly important due to its ability to convert CO into industrially valuable chemicals. To translate the potential of into technical applications, it is necessary to optimize and scale up production processes.

Synthesis, Fluorine-18 Radiolabeling, and In Vivo PET Imaging of a Hydrophilic Fluorosulfotetrazine.

The development of F-fluorotetrazines, suitable for the radiolabeling of biologics such as proteins and antibodies by IEDDA ligation, represents a major challenge, especially for pre-targeting applications. The hydrophilicity of the tetrazine has clearly become a crucial parameter for the performance of in vivo chemistry. In this study, we present the design, the synthesis, the radiosynthesis, the physicochemical characterization, the in vitro and in vivo stability, as well as the pharmacokinetics and the biodistribution determined by PET imaging in healthy animals of an original hydrophilic F-fluorosulfotetrazine.

Comparison of plasmid stabilization systems during heterologous isopropanol production in fed-batch bioreactor.

Strain robustness during production of recombinant molecules is of major interest to ensure bioprocess profitability. The heterogeneity of populations has been shown in the literature as a source of instability in bioprocesses. Thus, the heterogeneity of the population was studied by evaluating the robustness of the strains (stability of plasmid expression, cultivability, membrane integrity and macroscopic cell behavior) during well-controlled fedbatch cultures.

Co-expression of an isopropanol synthetic operon and eGFP to monitor the robustness of Cupriavidus necator during isopropanol production.

Phenotypic heterogeneity in bioprocesses is suspected to reduce performances, even in case of monoclonal cultures. Here, robustness of an engineered isopropanol-overproducing strain and heterogeneity of its plasmid expression level were evaluated in fed-batch cultures. Previously, eGFP was identified as a promising plasmid expression reporter for C.

Study of plasmid-based expression level heterogeneity under plasmid-curing like conditions in Cupriavidus necator.

Plasmid expression level heterogeneity in Cupriavidus necator was studied in response to stringent culture conditions, supposed to enhance plasmid instability, through plasmid curing strategies. Two plasmid curing strategies were compared based on their efficiency at generating heterogeneity in batch: rifampicin addition and temperature increase. A temperature increase from 30° to 37 °C was the most efficient plasmid curing strategy.

Investigation of the robustness of Cupriavidus necator engineered strains during fed-batch cultures.

It is of major interest to ensure stable and performant microbial bioprocesses, therefore maintaining high strain robustness is one of the major future challenges in industrial microbiology. Strain robustness can be defined as the persistence of genotypic and/or phenotypic traits in a system. In this work, robustness of an engineered strain is defined as plasmid expression stability, cultivability, membrane integrity and macroscopic cell behavior and was assessed in response to implementations of sugar feeding strategies (pulses and continuous) and two plasmid stabilization systems (kanamycin resistance and Post-Segregational Killing hok/sok).

Accelerostat study in conventional and microfluidic bioreactors to assess the key role of residual glucose in the dimorphic transition of Yarrowia lipolytica in response to environmental stimuli.

Yarrowia lipolytica, with a diverse array of biotechnological applications, is able to grow as ovoid yeasts or filamentous hyphae depending on environmental conditions. This study has explored the relationship between residual glucose levels and dimorphism in Y. lipolytica.

Insights into Clostridium tetani: From genome to bioreactors.

Tetanus vaccination is of major importance for public health in most countries in the world. The World Health Organization indicated that 15,000 tetanus cases were reported in 2018 (Organization, World Health, 2019). Currently, vaccine manufacturers use tetanus toxin produced by Clostridium tetani fermentation in complex media.

Plasmid expression level heterogeneity monitoring via heterologous eGFP production at the single-cell level in Cupriavidus necator.

A methodology for plasmid expression level monitoring of eGFP expression suitable for dynamic processes was assessed during fermentation. This technique was based on the expression of a fluorescent biosensor (eGFP) encoded on a recombinant plasmid coupled to single-cell analysis. Fluorescence intensity at single-cell level was measured by flow cytometry.

Nutritional, biochemical and microbiological composition of Mart. sap in Burkina Faso.

The palmyra palm Mart. grow wild and gives natural stands in several localities of central-eastern and eastern regions of Burkina Faso. This work aimed to determine the nutritional, biochemical and microbiological composition of fresh palm sap from Mart.

Isopropanol production from carbon dioxide in Cupriavidus necator in a pressurized bioreactor.

A bioreactor was designed to provide high gas mass transfer to reach cell and product titres in the g L level from CO for realistic, laboratory scale, engineered autotrophic strain evaluation. The design was based on independent CO, H and air inputs and the ability to operate at high pressures. The bioreactor configuration and cultivation strategy enabled growth of Cupriavidus necator strains for long periods, to reach over 3 g L dry cell weight.

[F]Fludarabine-PET as a promising tool for differentiating CNS lymphoma and glioblastoma: Comparative analysis with [F]FDG in human xenograft models.

This paper investigated whether positron emission tomography (PET) imaging with [F]fludarabine ([F]FDB) can help to differentiate central nervous system lymphoma (CNSL) from glioblastoma (GBM), which is a crucial issue in the diagnosis and management of patients with these aggressive brain tumors. Multimodal analyses with [F]fluorodeoxyglucose ([F]FDG), magnetic resonance imaging (MRI) and histology have also been considered to address the specificity of [F]FDB for CNSL. Nude rats were implanted with human MC116 lymphoma-cells (n = 9) or U87 glioma-cells (n = 4).

Alka(e)ne synthesis in Cupriavidus necator boosted by the expression of endogenous and heterologous ferredoxin-ferredoxin reductase systems.

To boost aldehyde deformylating oxygenase (ADO) activity in a Cupriavidus necator strain expressing a synthetic alkane pathway, the expression of two ferredoxin-ferredoxin reductase systems was tested. The genes of a native fd/FNR-like system were identified in C. necator and expressed in a previously engineered alka(e)ne producing strain.

Impacts of environmental conditions on product formation and morphology of Yarrowia lipolytica.

The yeast Yarrowia lipolytica is an industrially important microorganism with distinctive physiological and metabolic characteristics. A variety of external factors (e.g.

F-Fludarabine PET for Lymphoma Imaging: First-in-Humans Study on DLBCL and CLL Patients.

This was the first-in-humans clinical study of F-fludarabine, which is a radiopharmaceutical for PET imaging in lymphoma, for which many issues remain controversial with the standard radiotracer F-FDG. F-fludarabine PET or PET/CT was performed on 10 patients: 5 with diffuse large B-cell lymphoma (DLBCL) and 5 with chronic lymphocytic leukemia. The tumor uptake, biodistribution, and radiation dosimetry of F-fludarabine were evaluated.

Modeling and optimization of lipid accumulation by Yarrowia lipolytica from glucose under nitrogen depletion conditions.

Oleaginous yeasts have been seen as a feasible alternative to produce the precursors of biodiesel due to their capacity to accumulate lipids as triacylglycerol having profiles with high content of unsaturated fatty acids. The yeast Yarrowia lipolytica is a promising microorganism that can produce lipids under nitrogen depletion conditions and excess of the carbon source. However, under these conditions, this yeast also produces citric acid (overflow metabolism) decreasing lipid productivity.

Modulation of the Glycerol Phosphate availability led to concomitant reduction in the citric acid excretion and increase in lipid content and yield in Yarrowia lipolytica.

In order to improve TriAcylGycerol (TAG) lipids accumulation in the yeast Yarrowia lipolytica on glucose, double over-expression of the major acyl-CoA:diacylglycerol acyltransferase encoding gene (ylDGA2) and of the glycerol-phosphate dehydrogenase encoding gene (ylGPD1) was carried out. The genes were over-expressed in a strain impaired for the mobilization of the accumulated lipids, through the deletion of the genes encoding acyl-coenzyme A oxidases (POX1-6 genes) and the deletion of the very efficient lipase attached to the lipid bodies, encoded by ylTGL4. This metabolic engineering strategy had the objective of pulling the C-flow into the TAG synthesis by increasing the availability of glycerol-3-phosphate and its binding to fatty acids for the TAG synthesis.

Expanding the genetic tool box for Cupriavidus necator by a stabilized L-rhamnose inducible plasmid system.

The Gram negative bacterium Cupriavidus necator is well known for the accumulation of poly(3-hydroxybutyrate) and its fast lithoautotrophic growth, leading in high cell densities. Although the host was engineered for the heterologous production of diverse chemicals and biopolymers in recent years, tool box of stabilized inducible expression systems is still limited. To avoid plasmid loss during fermentation processes and to allow expression of complex proteins, a tunable L-rhamnose inducible system was established and characterized using enhanced green fluorescent protein (eGFP).