Get to Know Your Neighbors: Characterization of Close Isolates and Toxin Profile Diversity in the Group.

Unexpected atypical isolates of occasionally challenge conventional microbiology and even the most advanced techniques for anthrax detection. For anticipating and gaining trust, 65 isolates of of diverse origin were sequenced and characterized. The BTyper3 tool was used for assignation to genomospecies (34), (29) and (2), as well as virulence factors and toxin profiling.

Hydrogen Peroxide Vapor Decontamination of Hazard Group 3 Bacteria and Viruses in a Biosafety Level 3 Laboratory.

Aim: This study aimed to validate the efficacy of hydrogen peroxide vapor (HPV) decontamination technology set up in a biosafety level 3 (BSL-3) laboratory on surrogates and hazard group 3 (HG3) agents.

Methods And Results: The HPV decontamination system (Bioquell) was assessed with both qualitative and quantitative methods on (1) spore surrogates (, , and ) in the BSL-3 laboratory and in the material airlock and on (2) HG3 agents ( SARS-CoV-2, Venezuelan equine encephalitis virus [VEE], and Vaccinia virus) in the BSL-3 laboratory. Other HG3 bacteria likely to be handled in the BSL-3 laboratory (, , , and ) were excluded from the HPV decontamination assays as preliminary viability tests demonstrated the total inactivation of these agents after 48 h drying on different materials.

Lessons learned from the investigation of a COVID-19 cluster in Creil, France: effectiveness of targeting symptomatic cases and conducting contact tracing around them.

Background: This study presents the methods and results of the investigation into a SARS-CoV-2 outbreak in a professional community. Due to the limited testing capacity available in France at the time, we elaborated a testing strategy according to pre-test probability.

Methods: The investigation design combined active case finding and contact tracing around each confirmed case with testing of at-risk contact persons who had any evocative symptoms (n = 88).

Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent.

We report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1, a multi-partners transmembrane receptor overexpressed in numerous tumors, and thereby validated as promising target in oncology. The preparation of NRPa-308 proved challenging because of the orthogonality of the amide and sulphonamide bonds formation.

Neuropilin-1 peptide-like ligands with proline mimetics, tested using the improved chemiluminescence affinity detection method.

Many reports have suggested that NRP-1 acts as a co-receptor for VEGF-A and boosts tumour growth and metastasis. This NRP-1, due to its important role in tumour progression, triggered interest in the design of new molecules able to significantly inhibit NRP-1/VEGF-A interaction to suppress pathological angiogenesis. Our previous SAR studies of compounds, showing affinity for NRP-1, led us to develop branched peptides with general formula Lys(hArg)-AA-AA-Arg.

NRPa-308, a new neuropilin-1 antagonist, exerts in vitro anti-angiogenic and anti-proliferative effects and in vivo anti-cancer effects in a mouse xenograft model.

Neuropilin-1 (NRP-1) is an extra-cellular receptor for the main Vascular Endothelial Growth Factor over-expressed in tumour tissues, VEGF-A. Consequently, NRP-1 is involved in angiogenesis and in tumour growth, and its over-expression is related to a clinical poor prognosis. NRP-1 appears as a major target in oncology, which remains poorly exploited.

APN/CD13 is over-expressed by Psoriatic fibroblasts and is modulated by CGRP and IL-4 but not by retinoic acid treatment.

Psoriasis vulgaris is a common skin inflammatory disease characterized by recurrent flare episodes associated with scaly well-demarcated skin plaques. Skin biopsies from psoriatic patients with high PASI score (22.67 ± 8.

Disruption of phactr-1 pathway triggers pro-inflammatory and pro-atherogenic factors: New insights in atherosclerosis development.

Significant interest has recently emerged for phosphatase and actin regulatory protein (PHACTR1) gene in heart diseases prognosis. However, the functional role of phactr-1 protein remains elusive in heart related-diseases such as atherosclerosis, coronary artery calcification, ischaemic stroke, coronary artery stenosis and early-onset myocardial infarction. Phactr-1 is directly regulated by vascular endothelial growth factor A165 (VEGF-A165) through VEGF receptor 1 (VEGR-1) and Neuropilin-1 (NRP-1).

Conformational analysis of a polyconjugated protein-binding ligand by joint quantum chemistry and polarizable molecular mechanics. Addressing the issues of anisotropy, conjugation, polarization, and multipole transferability.

We investigate the conformational properties of a potent inhibitor of neuropilin-1, a protein involved in cancer processes and macular degeneration. This inhibitor consists of four aromatic/conjugated fragments: a benzimidazole, a methylbenzene, a carboxythiourea, and a benzene-linker dioxane, and these fragments are all linked together by conjugated bonds. The calculations use the SIBFA polarizable molecular mechanics procedure.

Synthesis and structure-activity relationship of non-peptidic antagonists of neuropilin-1 receptor.

Neuropilins (NRPs) are VEGF-A165 co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A165/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1.

Yersinia pseudotuberculosis ST42 (O:1) Strain Misidentified as Yersinia pestis by Mass Spectrometry Analysis.

We report here the draft sequence of strain CEB14_0017, alias HIAD_DUP, recovered from a human patient and initially identified as Yersinia pestis by mass spectrometry analysis. Genotyping based on tandem repeat polymorphism assigned the strain to Yersinia pseudotuberculosis sequence type 42 (ST42). The total assembly length is 4,894,739 bp.

Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model.

Neuropilin-1/-2 (+33 NRPs), VEGF-A165 co-receptors, are over-expressed during cancer progression. Thus, NRPs targeted drug development is challenged using a multistep in silico/in vitro screening procedure. The first fully non-peptidic VEGF-A165/NRPs protein-protein interaction antagonist (IC50=34 μM) without effect on pro-angiogenic kinases has been identified (compound-1).

Inhibition of both focal adhesion kinase and fibroblast growth factor receptor 2 pathways induces anti-tumor and anti-angiogenic activities.

FAK and FGFR2 signaling pathways play important roles in cancer development, progression and tumor angiogenesis. PHM16 is a novel ATP competitive inhibitor of FAK and FGFR2. To evaluate the therapeutic efficacy of this agent, we examined its anti-angiogenic effect in HUVEC and its anti-tumor effect in different cancer cell lines.

New biologically active hydrogen sulfide donors.

Generous donors: The dithioperoxyanhydrides (CH3 COS)2 , (PhCOS)2 , CH3 COSSCO2 Me and PhCOSSCO2 Me act as thiol-activated hydrogen sulfide donors in aqueous buffer solution. The most efficient donor (CH3 COS)2 can induce a biological response in cells, and advantageously replace hydrogen sulfide in ex vivo vascular studies.

Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity.

We report herein the synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK (focal adhesion kinase) inhibitors and the evaluation of their anti-angiogenic activity on HUVEC cells. Generally, the effects of these compounds on endothelial cells could be correlated with their kinase inhibitory activity. The most efficient compounds displayed inhibition of viability against HUVEC cells in the micromolar range, as observed with TAE-226, which was designed by Novartis Pharma AG.

Human Muscle Progenitor Cells Displayed Immunosuppressive Effect through Galectin-1 and Semaphorin-3A.

In human skeletal muscle, myoblasts represent the main population of myogenic progenitors. We previously showed that, beside their myogenic differentiation capacities, myoblasts also differentiate towards osteogenic and chondrogenic lineages, some properties generally considered being hallmarks of mesenchymal stem cells (MSCs). MSCs are also characterized by their immunosuppressive potential, through cell-cell contacts and soluble factors, including prostaglandin E-2 (PGE-2), transforming growth factor-β1 (TGF-β1), interleukine-10, or indoleamine 2,3-dioxygenase.

Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells.

Recently, we identified a new Vascular Endothelial Growth Factor (VEGF)-A(165)-induced gene Phactr-1, (Phosphatase Actin Regulator-1). We reported that Phactr-1 gene silencing inhibited tube formation in human umbilical endothelial cells (HUVECs) indicating a key role for Phactr-1 in tubulogenesis in vitro. In this study, we investigated the role of Phactr-1 in several cellular processes related to angiogenesis.

Depletion of the novel protein PHACTR-1 from human endothelial cells abolishes tube formation and induces cell death receptor apoptosis.

Using suppression subtractive hybridisation (SSH), we identified a hitherto unreported gene PHACTR-1 (Phosphatase Actin Regulating Protein-1) in Human Umbilical Vascular Endothelial Cells (HUVECs). PHACTR-1 is an actin and protein phosphatase 1 (PP1) binding protein which is reported to be highly expressed in brain and which controls PP1 activity and F-actin remodelling. We have also reported that its expression is dependent of Vascular Endothelial Growth Factor (VEGF-A(165)).

Economic evaluation of a 100% whey-based, partially hydrolysed formula in the prevention of atopic dermatitis among French children.

Objective: A pharmacoeconomic analysis was performed to determine costs, consequences and cost effectiveness of a partially hydrolysed 100% whey-based infant formula, NAN HA, manufactured by Nestlé S.A, Switzerland (PHF-W) and branded under Nidal Excel HA in France, in the prevention of atopic dermatitis (AD) in 'at risk' children when compared to standard cows' milk formula (SF) in France.

Methods: A decision-analytic economic model depicting AD treatment pathways, as well as resource utilisation and costs associated with the treatment of AD in healthy yet 'at risk' French newborns who cannot be exclusively breastfed was constructed for a 12-month time horizon, including an initial 6 months of intervention with formula consumption.

Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs).

Microbial infection triggers the endogenous production of immunosuppressive glucocorticoid (GC) hormones and simultaneously activates innate immunity through toll-like receptors (TLRs). How innate immune cells integrate these 2 opposing signals in dictating immunity or tolerance to infection is not known. In this study, we show that human plasmacytoid predendritic cells (pDCs) were highly sensitive to GC-induced apoptosis.

RasV12 induces Survivin/AuroraB pathway conferring tumor cell apoptosis resistance.

Several cancers are treated by interferons alpha and gamma in association with conventional chemotherapy due to the resistance observed with interferon treatment alone. The frequency of un-sensitive cancer depends on tumor origin and oncogenic genes. Preclinical studies have highlighted interferon resistance in many cancers such as colon carcinoma due to oncogenic Ras.

Free HTLV-1 induces TLR7-dependent innate immune response and TRAIL relocalization in killer plasmacytoid dendritic cells.

A recent report demonstrated that free human T-cell leukemia virus 1 (HTLV-1) could infect plasmacytoid dendritic cells (pDCs). The major role of pDCs is to secrete massive levels of interferon-alpha (IFN-alpha) upon virus exposure; however, the induction of IFN-alpha by HTLV-1 remains unknown. We demonstrate here that cell-free HTLV-1 generated a pDC innate immune response by producing massive levels of IFN-alpha that were inhibited by anti-HTLV-1 antibodies.

p120-Ras GTPase activating protein (RasGAP): a multi-interacting protein in downstream signaling.

p120-RasGAP (Ras GTPase activating protein) plays a key role in the regulation of Ras-GTP bound by promoting GTP hydrolysis via its C-terminal catalytic domain. The p120-RasGAP N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains. These protein domains allow various functions, such as anti-/pro-apoptosis, proliferation and also cell migration depending of their distinct partners.

Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12) oncogenic cells: modulation of cell survival and migration.

Ras GTPase-activating protein (RasGAP) is hypothesized to be an effector of oncogenic Ras stimulating numerous downstream cellular signaling cascades involved in survival, proliferation and motility. In this study, we identified calpain small subunit-1 (Capns1) as a new RasGAP-SH3 domain binding partner, using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation assay and was found specific to cells expressing oncogenic K-Ras.