Molecular Signature of Polyoxometalates in Electron Transport of Silicon-based Molecular Junctions

Polyoxometalates (POMs) are unconventional electro-active molecules with a great potential for applications in molecular memories, providing efficient processing steps onto electrodes are available. The synthesis of the organic-inorganic polyoxometalate hybrids [PM$_{11}$O$_{39}$(Sn(C$_6$H$_4$)C$\equiv$C(C$_6$H$_4$)N$_2$)]$^{3-}$ (M = Mo, W) endowed with a remote diazonium function is reported together with their covalent immobilization onto hydrogenated n-Si(100) substrates. Electron transport measurements through the resulting densely-packed monolayers contacted with a mercury drop as a top electrode confirms their homogeneity. Adjustment of the current-voltage curves with the Simmons equation gives a mean tunnel energy barrier of 1.8 eV and 1.6 eV, for the Silicon-Molecules-Metal (SMM) junctions based on the polyoxotungstates (M = W) and polyoxomolybdates (M = Mo), respectively. This follows the trend observed in the electrochemical properties of POMs in solution, the polyoxomolybdates being easier to reduce than the polyoxotungstates, in agreement with lowest unoccupied molecular orbitals (LUMOs) of lower energy. The molecular signature of the POMs is thus clearly identifiable in the solid-state electrical properties and the unmatched diversity of POM molecular and electronic structures should offer a great modularity

Late vaccination reinforcement during a measles epidemic in Niamey, Niger (2003-2004).

Low measles vaccination coverage (VC) leads to recurrent epidemics in many African countries. We describe VC before and after late reinforcement of vaccination activities during a measles epidemic in Niamey, Niger (2003-2004) assessed by Lot Quality Assurance Sampling (LQAS). Neighborhoods of Niamey were grouped into 46 lots based on geographic proximity and population homogeneity. Before reinforcement activities, 96% of lots had a VC below 70%. After reinforcement, this proportion fell to 78%. During the intervention 50% of children who had no previous record of measles vaccination received their first dose (vaccination card or parental recall). Our results highlight the benefits and limitations of vaccine reinforcement activities performed late in the epidemic

Effects of a soluble dietary fibre NUTRIOSE® on colonic fermentation and excretion rates in rats

The resistant dextrin NUTRIOSE®, developed from starch, is expected to act as a prebiotic. The aim of this study was to determine the effects of NUTRIOSE® on cecal parameters, short-chain fatty acid (SCFA) concentrations, and fecal excretion in rats. In an initial experiment, twenty-four male Fischer F344 rats were randomly assigned to one of the following four treatments for 14 days: G0 (control diet), G2.5 (control diet + 2.5% of dextrin), G5 (control diet + 5% of dextrin), and G10 (control diet + 10% of dextrin). After 14 days, total cecal weight, cecal content, and cecal wall weight were significantly increased in G5 and G10 compared to G0. At the same time, cecal pH was significantly lower in G10 compared to G0. Total SCFA concentration was significantly higher in G10 than in G5, G2.5, and G0, and significantly higher in G5 than in G0. Acetate, butyrate, and propionate concentrations were significantly increased in G5 and G10 compared to the controls. In a second trial based on a similar design, eighteen male Fischer F344 rats were treated with a control diet supplemented with 5% of dextrin or 5% of fructo-oligosaccharide. The results obtained with NUTRIOSE® were similar to those obtained with the fructo-oligosaccharide. In a third experiment, two groups of 5 Fischer F344 rats were orally treated with 100 and 1,000 mg/kg NUTRIOSE®, respectively, and from 18% to 25% of the dextrin was excreted in the feces. The results of these three studies show that the consumption of NUTRIOSE®, by its effects on total cecal weight, cecal content, cecal wall weight, pH, and SCFA production, could induce healthy benefits since these effects are reported to be prebiotic effects

Overview of grapevine trunk diseases in France in the 2000s

The National Grapevine Trunk Disease Survey was conducted in France from 2003 to 2008 to monitor grapevine trunk diseases (GTDs), eutypa dieback and esca/black dead arm (BDA). Data collected from seven regions, 329 vineyards and 12 cultivars were analysed. There were great variations amongst regions in the incidence of GTDs. For esca/BDA, two groups were distinguished: vineyards in Jura and Charentes had greater incidence (93–95%) than those of Bordeaux, Alsace and Bourgogne (54–82%). Incidence increased in Charentes over the 6-year survey, with the highest values being recorded during the last 2 years. For eutypa dieback, all vineyards of Charentes were affected, with 17 to 25% of vines expressing symptoms; for the other regions, 52 to 80% of vineyards were affected, with incidences below 3%. Cultivars Savagnin and Trousseau in Jura were especially affected by esca/BDA. Instead, Ugni Blanc in Charentes was most affected by eutypa dieback. One cultivar could be significantly more affected in one region than in another. The global health status of the vineyards was also investigated. (i) For four regions, 82% (Jura) to 87% (Alsace) of the grapevines were healthy, but this percentage decreased steadily (67%) in Charentes. (ii) Plants infected by GTDs were 32 and 18% in Jura and Charentes respectively, and only 2.9% in the Bourgogne region. (iii) The unproductive plants, i.e. dead, missing, replanted or restored, represented a significant part of the losses (6.6% in Charentes to 9.9% in Jura). The extension of GTDs is discussed with regard to the abiotic and biotic factors that may favour the diseases

Lemierre's syndrome and genetic polymorphisms: a case report

BACKGROUND: Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. CASE PRESENTATION: A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. CONCLUSION: The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology

Overview of grapevine trunk diseases in France in the 2000s

The National Grapevine Trunk Disease Survey was conducted in France from 2003 to 2008 to monitor grapevine trunk diseases (GTDs), eutypa dieback and esca/black dead arm (BDA). Data collected from seven regions, 329 vineyards and 12 cultivars were analysed. There were great variations amongst regions in the incidence of GTDs. For esca/BDA, two groups were distinguished: vineyards in Jura and Charentes had greater incidence (93–95%) than those of Bordeaux, Alsace and Bourgogne (54–82%). Incidence increased in Charentes over the 6-year survey, with the highest values being recorded during the last 2 years. For eutypa dieback, all vineyards of Charentes were affected, with 17 to 25% of vines expressing symptoms; for the other regions, 52 to 80% of vineyards were affected, with incidences below 3%. Cultivars Savagnin and Trousseau in Jura were especially affected by esca/BDA. Instead, Ugni Blanc in Charentes was most affected by eutypa dieback. One cultivar could be significantly more affected in one region than in another. The global health status of the vineyards was also investigated. (i) For four regions, 82% (Jura) to 87% (Alsace) of the grapevines were healthy, but this percentage decreased steadily (67%) in Charentes. (ii) Plants infected by GTDs were 32 and 18% in Jura and Charentes respectively, and only 2.9% in the Bourgogne region. (iii) The unproductive plants, i.e. dead, missing, replanted or restored, represented a significant part of the losses (6.6% in Charentes to 9.9% in Jura). The extension of GTDs is discussed with regard to the abiotic and biotic factors that may favour the diseases

JCO Clin Cancer Inform

PURPOSE: Many institutions throughout the world have launched precision medicine initiatives in oncology, and a large amount of clinical and genomic data is being produced. Although there have been attempts at data sharing with the community, initiatives are still limited. In this context, a French task force composed of Integrated Cancer Research Sites (SIRICs), comprehensive cancer centers from the Unicancer network (one of Europe's largest cancer research organization), and university hospitals launched an initiative to improve and accelerate retrospective and prospective clinical and genomic data sharing in oncology. MATERIALS AND METHODS: For 5 years, the OSIRIS group has worked on structuring data and identifying technical solutions for collecting and sharing them. The group used a multidisciplinary approach that included weekly scientific and technical meetings over several months to foster a national consensus on a minimal data set. RESULTS: The resulting OSIRIS set and event-based data model, which is able to capture the disease course, was built with 67 clinical and 65 omics items. The group made it compatible with the HL7 Fast Healthcare Interoperability Resources (FHIR) format to maximize interoperability. The OSIRIS set was reviewed, approved by a National Plan Strategic Committee, and freely released to the community. A proof-of-concept study was carried out to put the OSIRIS set and Common Data Model into practice using a cohort of 300 patients. CONCLUSION: Using a national and bottom-up approach, the OSIRIS group has defined a model including a minimal set of clinical and genomic data that can be used to accelerate data sharing produced in oncology. The model relies on clear and formally defined terminologies and, as such, may also benefit the larger international community

NF-kappa B genes have a major role in Inflammatory Breast Cancer

<p>Abstract</p> <p>Background</p> <p>IBC (Inflammatory Breast cancer) is a rare form of breast cancer with a particular phenotype. New molecular targets are needed to improve the treatment of this rapidly fatal disease. Given the role of NF-κB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC.</p> <p>Methods</p> <p>We measured the mRNA expression levels of 60 NF-κB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. Twenty-four distant metastases of breast cancer served as "poor prognosis" breast tumor controls.</p> <p>Results</p> <p>Thirty-five (58%) of the 60 NF-κB-related genes were significantly upregulated in IBC compared with non IBC. The upregulated genes were NF-κB genes (<it>NFKB1</it>, <it>RELA</it>, <it>IKBKG</it>, <it>NFKBIB</it>, <it>NFKB2</it>, <it>REL</it>, <it>CHUK</it>), apoptosis genes (<it>MCL1L</it>, <it>TNFAIP3/A20</it>, <it>GADD45B</it>, <it>FASLG</it>, <it>MCL1S</it>, <it>IER3L</it>, <it>TNFRSF10B/TRAILR2</it>), immune response genes (<it>CD40</it>, <it>CD48</it>, <it>TNFSF11/RANKL</it>, <it>TNFRSF11A/RANK</it>, <it>CCL2/MCP-1</it>, <it>CD40LG</it>, <it>IL15</it>, <it>GBP1</it>), proliferation genes (<it>CCND2</it>, <it>CCND3</it>, <it>CSF1R</it>, <it>CSF1</it>, <it>SOD2</it>), tumor-promoting genes (<it>CXCL12</it>, <it>SELE</it>, <it>TNC</it>, <it>VCAM1</it>, <it>ICAM1</it>, <it>PLAU/UPA</it>) or angiogenesis genes (<it>PTGS2/COX2</it>, <it>CXCL1/GRO1</it>). Only two of these 35 genes (<it>PTGS2/COX2 </it>and <it>CXCL1/GRO1</it>)were also upregulated in breast cancer metastases. We identified a five-gene molecular signature that matched patient outcomes, consisting of <it>IL8 </it>and <it>VEGF </it>plus three NF-κB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC.</p> <p>Conclusion</p> <p>The NF-κB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. Some upregulated NF-κB-related genes might serve as novel therapeutic targets in IBC.</p

Consolidation of an Olfactory Memory Trace in the Olfactory Bulb Is Required for Learning-Induced Survival of Adult-Born Neurons and Long-Term Memory

Background: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Methodology/Principal Findings: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. Conclusion/Significance: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival durin

BMC Med

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates