Activation peptide of the coagulation factor XIII (AP-F13A1) as a new biomarker for the screening of colorectal cancer

International audienceBackground: Colorectal cancer (CRC) remains a major cause of cancer fatalities in developed countries. The risk of death is correlated to the stage of CRC during the primary diagnosis. Early diagnosis is closely associated with enhanced survival rate. We therefore investigated the AP-F13A1 as a potential protein marker of CRC. Methods: The protein expression of FXIII in 40 serum samples was evaluated by enzyme-linked immunosorbent assays. Additionally, targeted proteomic assays (LC-PRM) were used to evaluate the expression of the activation peptide of F13A1 (AP-F13A1) in a further 113 serum samples. Results were analyzed by the Wilcoxon test and receiver operating characteristic curves generated to assess statistical differences and diagnostic factors between CRC patients and controls. Results: AP-F13A1 was quantified in human serum samples using calibration curves with excellent linearity. AP-F13A1 was reduced in CRC patients using PRM assays from two distinct biobanks. The AUC for AP-F13A1 were 0.95 and 0.93. Sensitivity/specificity values for the two sets of patients were 75%/95% and 71%/95% respectively. Conclusion: We have presented the proof of principle that in vivo release of AP-F13A1 can be measured by PRM-based strategies in CRC serum samples. AP-F13A1 may be an effective serological biomarker as part of a screening program of CRC detection

Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

International audienceBackgroundNon-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients.MethodsWe used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination.ResultsFor Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82.ConclusionsWe showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction

IDENTIFICATION PAR CDNA DIFFERENTIAL DISPLAY DE NOUVEAUX GENES IMPLIQUES DANS L'APOPTOSE INDUITE PAR LA PROTEINE P53 ETUDE FONCTIONNELLE DE LA PROTEINE HUMSIAH ET DE LA PRESENILINE-1 DANS LA SUPPRESSION TUMORALE

PARIS-BIUSJ-Physique recherche (751052113) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Surface vitrification caused by natural fires in Late Pleistocene wetlandsof the Atacama Desert

International audienceMelted rocks are a common feature in many of the 175 recognized terrestrial impact structures [1]. However, someglasses, like the Dakhleh Glass [2] or the Edeowie Glass [3] are also attributed to impacts despite the lack of otherdirect evidence. These cases have been attributed to low-altitude airbursts of cosmic bodies (asteroids, comets)during their entry in the Earth’s atmosphere but the identification and mechanism of formation of these glasses arehowever debated.Massive glass blocks were recently discovered [4] in the Tamarugal-Llamara basin of the Atacama desert in Chile.We show that these glasses, found near the town of Pica at four localities separated by up to 70 km, are neitherfulgurites, nor volcanic glasses, nor metallurgical slags related to anthropic activity, but show close similaritieswith other glasses, which have been attributed to large airbursts. However, most glasses contain numerous plantimprints and some glasses are mainly made of partially melted silicified plant twigs and field observations indicatethat the glasses are restricted to specific Late Pleistocene wetlands. Large oases did indeed form in the hyperaridAtacama desert due to elevated groundwater discharge and increased recharge during the Central Andean PluvialEvent (roughly coeval with the Mystery interval and Younger Dryas). 14C dating and paleomagnetic dataindicate that the glasses were formed during at least two distinct periods. The strong environmental control onthe distribution of the glasses and large differences in ages rule out the hypothesis of a single large airburst asthe cause of surface melting. The available data suggest that the Atacama desert surface glasses were formedin situ by natural fires in soils rich in dry organic matter and siliceous biological remains, at a time of strongclimate oscillations between wet (organic matter accumulation in soils) and dry periods (triggering fires) in desertwetlands.Our interpretation likely applies to other cases of silicate glasses attributed to airbursts, challenging the highairburst rate as well as the interpretation of fossils and organic matter in “impact glasses” [5]. Our study alsodemonstrates that exotic mineralogy with glass containing spherules of iron sulphides, metallic iron or ironphosphides may not necessarily imply an impact origin. This in turn cast doubts on some studies relating impactand climate change triggering the Younger Dryas cold event at the end of the Pleistocene [6].1. French, B. M. & Koeberl, C. Earth-Sci. Rev. 98, 123–170 (2010).2. Osinski, G. R. et al. Meteorit. Planet. Sci. 43, 2089–2107 (2008).3. Haines, P. W., Jenkins, R. J. F. & Kelley, S. P. Geology 29, 899 (2001).4. Blanco, N. & Tomlinsson, A. J. Carta Guatacondo, Región de Tarapacá. (2013).5. Schultz, P. H., Harris, R. S., Clemett, S. J., Thomas-Keprta, K. L. & Zarate, M. Geology 42, 515–518 (2014).6. Firestone, R. B. et al. Proc. Natl. Acad. Sci. 104, 16016–16021 (200

Surface vitrification caused by natural fires in Late Pleistocene wetlandsof the Atacama Desert

International audienceMelted rocks are a common feature in many of the 175 recognized terrestrial impact structures [1]. However, someglasses, like the Dakhleh Glass [2] or the Edeowie Glass [3] are also attributed to impacts despite the lack of otherdirect evidence. These cases have been attributed to low-altitude airbursts of cosmic bodies (asteroids, comets)during their entry in the Earth’s atmosphere but the identification and mechanism of formation of these glasses arehowever debated.Massive glass blocks were recently discovered [4] in the Tamarugal-Llamara basin of the Atacama desert in Chile.We show that these glasses, found near the town of Pica at four localities separated by up to 70 km, are neitherfulgurites, nor volcanic glasses, nor metallurgical slags related to anthropic activity, but show close similaritieswith other glasses, which have been attributed to large airbursts. However, most glasses contain numerous plantimprints and some glasses are mainly made of partially melted silicified plant twigs and field observations indicatethat the glasses are restricted to specific Late Pleistocene wetlands. Large oases did indeed form in the hyperaridAtacama desert due to elevated groundwater discharge and increased recharge during the Central Andean PluvialEvent (roughly coeval with the Mystery interval and Younger Dryas). 14C dating and paleomagnetic dataindicate that the glasses were formed during at least two distinct periods. The strong environmental control onthe distribution of the glasses and large differences in ages rule out the hypothesis of a single large airburst asthe cause of surface melting. The available data suggest that the Atacama desert surface glasses were formedin situ by natural fires in soils rich in dry organic matter and siliceous biological remains, at a time of strongclimate oscillations between wet (organic matter accumulation in soils) and dry periods (triggering fires) in desertwetlands.Our interpretation likely applies to other cases of silicate glasses attributed to airbursts, challenging the highairburst rate as well as the interpretation of fossils and organic matter in “impact glasses” [5]. Our study alsodemonstrates that exotic mineralogy with glass containing spherules of iron sulphides, metallic iron or ironphosphides may not necessarily imply an impact origin. This in turn cast doubts on some studies relating impactand climate change triggering the Younger Dryas cold event at the end of the Pleistocene [6].1. French, B. M. & Koeberl, C. Earth-Sci. Rev. 98, 123–170 (2010).2. Osinski, G. R. et al. Meteorit. Planet. Sci. 43, 2089–2107 (2008).3. Haines, P. W., Jenkins, R. J. F. & Kelley, S. P. Geology 29, 899 (2001).4. Blanco, N. & Tomlinsson, A. J. Carta Guatacondo, Región de Tarapacá. (2013).5. Schultz, P. H., Harris, R. S., Clemett, S. J., Thomas-Keprta, K. L. & Zarate, M. Geology 42, 515–518 (2014).6. Firestone, R. B. et al. Proc. Natl. Acad. Sci. 104, 16016–16021 (200

Glass Strewnfield Produced by Dry Vegetation Fires Rather than Airburst: A Case Study from Atacama

International audienceWe described in [1] extended occurrences of unusual silicate glass surface layers from the Atacama Desert(Chile). These glasses, found near the town of Pica at four localities separated by up to 70 km, are neither fulgurites,nor volcanic glasses, nor metallurgical slags related to anthropic activity, but show close similarities to other glassesthat have been previously attributed to large airbursts created by meteoroids entering the Earth’s atmosphere. Theglasses are restricted to specific Late Pleistocene terrains: paleo-wetlands and soils rich in organic matter with SiO2-rich plant remains, salts and carbonates. 14C dating and paleomagnetic data indicate that the glasses were formedduring at least two distinct periods in the 12 to 15 ka interval. This rules out the hypothesis of a single large airburstas the cause of surface melting. Instead, burning of organic-rich soils in dried-out grassy wetlands during climateoscillations between wet and dry periods can account for the formation of the Pica glasses.The reducing combustion condition produced iron sulphides, phosphides, carbides and metal droplets in theglass; these are usually taken as evidence for ET contamination, but no trace of Ni or other highly siderophile elements(e.g. Ir, Pt) were detected. Plant imprints are numerous in the Pica glass, as observed in the Dakhleh (Egypt),Pampa (Argentina) and Edowie (Australia) glasses of presumed impact origin [2-4]. As for Pica, the glass distributionappears restricted to the paleohumid depressions in both Edowie and Dakhleh cases. In case of an airburst thistopographic control cannot be explained. We therefore propose to reevaluate previously published evidence for glassstrewnfields attributed to airbursts [2-5] in the light of the Pica glass study

Paleomagnetism and Mineralogy of Unusual Silicate Glasses and Baked Soils on the Surface of the Atacama Desert of Northern Chile: A Major Airburst Impact ~12ka ago?

International audienceUnusual silicate glasses were found in northern Chile in one of the driest place on earth, the Atacama Desert. The scoria-type melted rocks are littered on the ground at several localities distributed along a longitudinal band of about 50km. The silicate glasses have a stable natural remanent magnetization carried by fine-grained magnetite and acquired during cooling. At one locality, fine-grained overbank sediments were heated to form a 10 to 20 cm-thick layer of brick-type samples. Magnetic experiments on oriented samples demonstrate that the baked clays record a thermoremanent magnetization acquired in situ above 600°C down to more than 10cm depth and cooled under a normal polarity geomagnetic field with a paleointensity of 40µT. In some samples of the silicate glass, large grains of iron sulphides (troilite) are found in the glass matrix with numerous droplets of native iron, iron sulphides and iron phosphides indicating high temperature and strong redox conditions during melting. The paleomagnetic record of the baked clays and the unusual mineralogy of the silicate glasses indicate a formation mainly by in situ high temperature radiation. Paleomagnetic experiments and chemical analyses indicate that the silicate glasses are not fulgurite type rocks due to lightning events, nor volcanic glasses or even metallurgical slags related to mining activity. The existence of a well-developped baked clay layer indicates that the silicate glasses are not impact-related ejectas. The field, paleomagnetic and mineralogical observations support evidence for a thermal event likely related to a major airburst. The youngest calibrated 14C age on a charcoal sample closely associated with the glass indicates that the thermal event occurred around 12 to 13 ka BP. The good conservation of the surface effects of this thermal event in the Atacama Desert could provide a good opportunity to further estimate the threats posed by large asteroid airbursts

Glass Strewnfield Produced by Dry Vegetation Fires Rather than Airburst: A Case Study from Atacama

International audienceWe described in [1] extended occurrences of unusual silicate glass surface layers from the Atacama Desert(Chile). These glasses, found near the town of Pica at four localities separated by up to 70 km, are neither fulgurites,nor volcanic glasses, nor metallurgical slags related to anthropic activity, but show close similarities to other glassesthat have been previously attributed to large airbursts created by meteoroids entering the Earth’s atmosphere. Theglasses are restricted to specific Late Pleistocene terrains: paleo-wetlands and soils rich in organic matter with SiO2-rich plant remains, salts and carbonates. 14C dating and paleomagnetic data indicate that the glasses were formedduring at least two distinct periods in the 12 to 15 ka interval. This rules out the hypothesis of a single large airburstas the cause of surface melting. Instead, burning of organic-rich soils in dried-out grassy wetlands during climateoscillations between wet and dry periods can account for the formation of the Pica glasses.The reducing combustion condition produced iron sulphides, phosphides, carbides and metal droplets in theglass; these are usually taken as evidence for ET contamination, but no trace of Ni or other highly siderophile elements(e.g. Ir, Pt) were detected. Plant imprints are numerous in the Pica glass, as observed in the Dakhleh (Egypt),Pampa (Argentina) and Edowie (Australia) glasses of presumed impact origin [2-4]. As for Pica, the glass distributionappears restricted to the paleohumid depressions in both Edowie and Dakhleh cases. In case of an airburst thistopographic control cannot be explained. We therefore propose to reevaluate previously published evidence for glassstrewnfields attributed to airbursts [2-5] in the light of the Pica glass study