| 1. |
- Romagnoni, A, et al.
(author)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Journal article (peer-reviewed)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 2. |
- Acerbo, E, et al.
(author)
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Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers
- 2022
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In: Frontiers in neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16, s. 945221-
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Journal article (peer-reviewed)abstract
- Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 and 165 Hz, to various deep-seated targets, such as the Mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely an increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs).Materials and methodsIn the current study, we use Temporal Interference (TI) stimulation to provide a non-invasive DBS (130 Hz) of the MTL, specifically the hippocampus, in both mouse models of epilepsy, and scale the method using human cadavers to demonstrate the potential efficacy in human patients. Simulations for both mice and human heads were performed to calculate the best coordinates to reach the hippocampus.ResultsThis non-invasive DBS increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. We therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs. TCS in human cadavers. Results show a better penetration of TI fields into the human hippocampus as compared with TCS.SignificanceThese results constitute the first proof of the feasibility and efficiency of TI to stimulate at depth an area without impacting the surrounding tissue. The data tend to show the sufficiently focal character of the induced effects and suggest promising therapeutic applications in epilepsy.
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| 3. |
- Chen, Ping, et al.
(author)
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A 12.4-day periodicity in a close binary system after a supernova
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 253-258
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Journal article (peer-reviewed)abstract
- Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.
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| 4. |
- Sharma, Yashvi, et al.
(author)
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Dramatic Rebrightening of the Type-changing Stripped-envelope Supernova SN 2023aew
- 2024
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 966:2
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Journal article (peer-reviewed)abstract
- Multipeaked supernovae with precursors, dramatic light-curve rebrightenings, and spectral transformation are rare, but are being discovered in increasing numbers by modern night-sky transient surveys like the Zwicky Transient Facility. Here, we present the observations and analysis of SN 2023aew, which showed a dramatic increase in brightness following an initial luminous (−17.4 mag) and long (∼100 days) unusual first peak (possibly precursor). SN 2023aew was classified as a Type IIb supernova during the first peak but changed its type to resemble a stripped-envelope supernova (SESN) after the marked rebrightening. We present comparisons of SN 2023aew's spectral evolution with SESN subtypes and argue that it is similar to SNe Ibc during its main peak. P-Cygni Balmer lines are present during the first peak, but vanish during the second peak's photospheric phase, before Hα resurfaces again during the nebular phase. The nebular lines ([O i], [Ca ii], Mg i], Hα) exhibit a double-peaked structure that hints toward a clumpy or nonspherical ejecta. We analyze the second peak in the light curve of SN 2023aew and find it to be broader than that of normal SESNe as well as requiring a very high 56Ni mass to power the peak luminosity. We discuss the possible origins of SN 2023aew including an eruption scenario where a part of the envelope is ejected during the first peak and also powers the second peak of the light curve through interaction of the SN with the circumstellar medium.
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| 5. |
- Berthet, Gwenaël, et al.
(author)
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Impact of a moderate volcanic eruption on chemistry in the lower stratosphere : balloon-borne observations and model calculations
- 2017
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 17:3, s. 2229-2253
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Journal article (peer-reviewed)abstract
- The major volcanic eruption of Mount Pinatubo in 1991 has been shown to have significant effects on stratospheric chemistry and ozone depletion even at midlatitudes. Since then, only moderate but recurrent volcanic eruptions have modulated the stratospheric aerosol loading and are assumed to be one cause for the reported increase in the global aerosol content over the past 15 years. This particularly enhanced aerosol context raises questions about the effects on stratospheric chemistry which depend on the latitude, altitude and season of injection. In this study, we focus on the midlatitude Sarychev volcano eruption in June 2009, which injected 0.9 Tg of sulfur dioxide (about 20 times less than Pinatubo) into a lower stratosphere mainly governed by high-stratospheric temperatures. Together with in situ measurements of aerosol amounts, we analyse high-resolution in situ and/or remote-sensing observations of NO2, HNO3 and BrO from balloon-borne infrared and UV-visible spectrometers launched in Sweden in August-September 2009. It is shown that differences between observations and three-dimensional (3-D) chemistry-transport model (CTM) outputs are not due to transport calculation issues but rather reflect the chemical impact of the volcanic plume below 19 km altitude. Good measurement-model agreement is obtained when the CTM is driven by volcanic aerosol loadings derived from in situ or space-borne data. As a result of enhanced N2O5 hydrolysis in the Sarychev volcanic aerosol conditions, the model calculates reductions of similar to 45% and increases of similar to 11% in NO2 and HNO3 amounts respectively over the August-September 2009 period. The decrease in NOx abundances is limited due to the expected saturation effect for high aerosol loadings. The links between the various chemical catalytic cycles involving chlorine, bromine, nitrogen and HOx compounds in the lower stratosphere are discussed. The increased BrO amounts (similar to 22 %) compare rather well with the balloon-borne observations when volcanic aerosol levels are accounted for in the CTM and appear to be mainly controlled by the coupling with nitrogen chemistry rather than by enhanced BrONO2 hydrolysis. We show that the chlorine partitioning is significantly controlled by enhanced BrONO2 hydrolysis. However, simulated effects of the Sarychev eruption on chlorine activation are very limited in the high-temperature conditions in the stratosphere in the period considered, inhibiting the effect of ClONO2 hydrolysis. As a consequence, the simulated chemical ozone loss due to the Sarychev aerosols is low with a reduction of -22 ppbv (-1.5 %) of the ozone budget around 16 km. This is at least 10 times lower than the maximum ozone depletion from chemical processes (up to -20 %) reported in the Northern Hemisphere lower stratosphere over the first year following the Pinatubo eruption. This study suggests that moderate volcanic eruptions have limited chemical effects when occurring at midlatitudes (restricted residence times) and outside winter periods (high-temperature conditions). However, it would be of interest to investigate longer-lasting tropical volcanic plumes or sulfur injections in the wintertime low-temperature conditions.
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| 6. |
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| 7. |
- Hay-Schmidt, Anders, et al.
(author)
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Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour
- 2017
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In: Reproduction. - : Bioscientifica. - 1470-1626 .- 1476-3990. ; 154:2, s. 145-152
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Journal article (peer-reviewed)abstract
- Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDNPOA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.
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| 8. |
- Jégou, F., et al.
(author)
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Validation of Odin/SMR limb observations of ozone, comparisons with OSIRIS, POAM III, ground-based and balloon-borne intruments
- 2008
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:13, s. 3385-3409
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Journal article (peer-reviewed)abstract
- The Odin satellite carries two instruments capable of determining stratospheric ozone profiles by limb sounding: the Sub-Millimetre Radiometer (SMR) and the UV-visible spectrograph of the OSIRIS (Optical Spectrograph and InfraRed Imager System) instrument. A large number of ozone profiles measurements were performed during six years from November 2001 to present. This ozone dataset is here used to make quantitative comparisons with satellite measurements in order to assess the quality of the Odin/SMR ozone measurements. In a first step, we compare Swedish SMR retrievals version 2.1, French SMR ozone retrievals version 222 (both from the 501.8 GHz band), and the OSIRIS retrievals version 3.0, with the operational version 4.0 ozone product from POAM III (Polar Ozone Atmospheric Measurement). In a second step, we refine the Odin/SMR validation by comparisons with ground-based instruments and balloon-borne observations. We use observations carried out within the framework of the Network for Detection of Atmospheric Composition Change (NDACC) and balloon flight missions conducted by the Canadian Space Agency (CSA), the Laboratoire de Physique et de Chimie de l\'{}Environnement (LPCE, Orléans, France), and the Service d'Aéronomie (SA, Paris, France). Coincidence criteria were 5° in latitude×10° in longitude, and 5 h in time in Odin/POAM III comparisons, 12 h in Odin/NDACC comparisons, and 72 h in Odin/balloons comparisons. An agreement is found with the POAM III experiment (10–60 km) within −0.3±0.2 ppmv (bias±standard deviation) for SMR (v222, v2.1) and within −0.5±0.2 ppmv for OSIRIS (v3.0). Odin ozone mixing ratio products are systematically slightly lower than the POAM III data and show an ozone maximum lower by 1–5 km in altitude. The comparisons with the NDACC data (10–34 km for ozonesonde, 10–50 km for lidar, 10–60 for microwave instruments) yield a good agreement within −0.15±0.3 ppmv for the SMR data and −0.3±0.3 ppmv for the OSIRIS data. Finally the comparisons with instruments on large balloons (10–31 km) show a good agreement, within −0.7±1 ppmv. The official SMR v2.1 dataset is consistent in all altitude ranges with POAM III, NDACC and large balloon-borne instruments measurements. In the SMR v2.1 data, no different systematic error has been found in the 0–35km range in comparison with the 35–60 km range. The same feature has been highlighted in both hemispheres in SMR v2.1/POAM III intercomparisons, and no latitudinal dependence has been revealed in SMR v2.1/NDACC intercomparisons.
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| 9. |
- Mairal, A, et al.
(author)
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Characterization of a novel testicular form of human hormone-sensitive lipase
- 2002
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 291:2, s. 286-290
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Journal article (peer-reviewed)abstract
- Hormone-sensitive lipase (HSL) is an esterase and lipase, which are essential for spermatogenesis. Two HSL mRNAs are expressed in human testis. A long form is encoded by a testis-specific exon and nine exons common to testis and adipocyte HSL. Here we show that the short-form 3.3-kb mRNA possesses a unique 5' end that is transcribed from a novel testis-specific exon. The corresponding protein is similar to the 775-amino-acid-long adipocyte HSL. Immunohistochemistry experiments on human testis sections revealed that the long form is strictly expressed in haploid germ cells whereas the short form is expressed in interstitial and tubular somatic cells as well as premeiotic germ cells.
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| 10. |
- Martin, S., et al.
(author)
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SARS-CoV-2 integral membrane proteins shape the serological responses of patients with COVID-19
- 2021
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In: Iscience. - : Elsevier BV. - 2589-0042. ; 24:10
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Journal article (peer-reviewed)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has elicited a unique mobilization of the scientific community to develop efficient tools to understand and combat the infection. Like other coronavirae, SARS-CoV-2 hijacks host cell secretory machinery to produce viral proteins that compose the nascent virions; including spike (S), envelope (E), and membrane (M) proteins, the most exposed transmembrane proteins to the host immune system. As antibody response is part of the anti-viral immune arsenal, we investigate the immunogenic potential of S, E, and M using a human cell-based system to mimic membrane insertion and N-glycosylation. Both S and M elicit specific Ig production in patients with SARS-CoV-2. Patients with moderate and severe diseases exhibit elevated Ig responses. Finally, reduced Ig binding was observed with spike G614 compared to D614 variant. Altogether, our assay points toward an unexpected immune response against M and represents a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.
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