Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study

BACKGROUND: Synaptic dysfunction is an early core feature of Alzheimer's disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest. OBJECTIVE: To measure plasma NRG1 concentration in AD patients in comparison with other neurodegenerative disorders and neurological controls (NC) and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers. METHODS: This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n = 27) and at dementia stage (n = 35), non-AD dementia (n = 26, Aβ-negative), non-AD MCI (n = 19), and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (Aβ 42/Aβ 40 ratio, phospho-tau, and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25. RESULTS: Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P = 0.005 and P < 0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (β = 0.372, P = 0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in Aβ-positive patients (β = -0.197-0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin, and SNAP-25 (β = 0.278-0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in Aβ-positive patients (all, β = -0.188, P = 0.038; Aβ+: β = -0.255, P = 0.038). CONCLUSION: Plasma NRG1 concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD

H19 controls reactivation of the imprinted gene network during muscle regeneration

International audienceThe H19 locus controls fetal growth by regulating expression of several genes from the imprinted gene network (IGN). H19 is fully repressed after birth, except in skeletal muscle. Using loss-of-function H19(Delta 3) mice, we investigated the function of H19 in adult muscle. Mutant muscles display hypertrophy and hyperplasia, with increased Igf2 and decreased myostatin (Mstn) expression. Many imprinted genes are expressed in muscle stem cells or satellite cells. Unexpectedly, the number of satellite cells was reduced by 50% in H19(Delta 3) muscle fibers. This reduction occurred after postnatal day 21, suggesting a link with their entry into quiescence. We investigated the biological function of these mutant satellite cells in vivo using a regeneration assay induced by multiple injections of cardiotoxin. Surprisingly, despite their reduced number, the self-renewal capacity of these cells is fully retained in the absence of H19. In addition, we observed a better regeneration potential of the mutant muscles, with enhanced expression of several IGN genes and genes from the IGF pathway

Relaxation study of pre-densified silica glasses under 2.5 MeV electron irradiation

Abstract We examined the “relaxation properties” of pre-densified synthetic fused silica glass under 2.5 MeV electron irradiation. The densification of the glass was either obtained by hot compression (5 GPa-350 °C and 5 GPa-1000 °C) or via a thermal treatment increasing its fictive temperature (Tf = 1050, 1250 and 1400 °C). Under irradiation, the pre-densified silica glasses exhibit a relaxation of their macroscopic density with increasing integrated dose. Density was reduced for hot compressed silica and increased for Tf samples with different relaxation rates but it is remarkable that all sample densities follow a trend towards the same equilibrium value around 2.26 for a dose larger than 10 GGy despite a different final topology. After irradiation of hot compressed silica, the Raman spectra display a significant increment of 4 and almost 3-membered rings whereas they exhibit a glass density reduction; demonstrating that a D2 band increase cannot be considered as an absolute marker of the glass compaction. The correlation between density and D2 intensity remains valid until silica density remains lower than 2.26. In contrast, the FWHM of the main band peaking at 440 cm−1 appears to remain correlated to the silica glass density for all investigated samples

Cerebrospinal Fluid Alpha-Synuclein Improves the Differentiation between Dementia with Lewy Bodies and Alzheimer&rsquo;s Disease in Clinical Practice

Background: Alpha-synuclein, abnormally aggregated in Dementia with Lewy Bodies (DLB), could represent a potential biomarker to improve the differentiation between DLB and Alzheimer&rsquo;s disease (AD). Our main objective was to compare Cerebrospinal Fluid (CSF) alpha-synuclein levels between patients with DLB, AD and Neurological Control (NC) individuals. Methods: In a monocentric retrospective study, we assessed CSF alpha-synuclein concentration with a validated ELISA kit (ADx EUROIMMUN) in patients with DLB, AD and NC from a tertiary memory clinic. Between-group comparisons were performed, and Receiver Operating Characteristic analysis was used to identify the best CSF alpha-synuclein threshold. We examined the associations between CSF alpha-synuclein, other core AD CSF biomarkers and brain MRI characteristics. Results: We included 127 participants (mean age: 69.3 &plusmn; 8.1, Men: 41.7%). CSF alpha-synuclein levels were significantly lower in DLB than in AD (1.28 &plusmn; 0.52 ng/mL vs. 2.26 &plusmn; 0.91 ng/mL, respectively, p &lt; 0.001) without differences due to the stage of cognitive impairment. The best alpha-synuclein threshold was characterized by an Area Under the Curve = 0.85, Sensitivity = 82.0% and Specificity = 76.0%. CSF alpha-synuclein was associated with CSF AT(N) biomarkers positivity (p &lt; 0.01) but not with hippocampal atrophy or white matter lesions. Conclusion: CSF Alpha-synuclein evaluation could help to early differentiate patients with DLB and AD in association with existing biomarkers

Natural and anthropogenic dynamics of the coastal environment in northwestern Corsica (western Mediterranean) over the past six millennia

International audienceThe present paper provides new insights into the climatic and anthropic factors that influenced a 6000-year coastal evolution in northwestern Corsica, the third largest island of the western Mediterranean. Pollen, microcharcoal, sedimentary and geochemical analyses were carried out on a core drilled in the Crovani coastal wetland to reconstruct the regional drivers of landscape change. We show that anthropogenic and climate-induced fires favoured the development of Mediterranean maquis, dominated by Erica and Quercus ilex, from ca. 6000 to 3350 cal. BP. A change in arboreal vegetation triggered a short but intense sediment input in the Crovani pond between ca. 3350 and 3200 cal. BP. This is consistent with a coeval process of runoff recorded in several coastal sites of western Corsica and related to an arid climate change occurred in many sites of the western Mediterranean around 3200 years ago. We provide evidence of agriculture during the Late Neolithic from ca. 3900 BC, which is much earlier than any archaeological evidence previously available in this area of Corsica, followed by a progressive decline of arable farming practices. Human impact has been responsible for a degradation of the maquis only from approximately 3000 cal. BP, and it intensified in Roman times, when the area experienced the first phase of galena exploitation from the Argentella mines. Over the last 500 years, the present work evidences a major development of Castanea related to cultivation during the Genoese administration of Corsica. Our findings suggest that solar activity and the North Atlantic Oscillation had an influence on centennial-scale forest cover variations during the last 6000 years

Plasma neurofilament light chain in memory clinic practice: Evidence from a real-life study

Objective: To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice. Methods: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology. The patients' biomarker data were examined for associations with: i/cognitive status ii/presence of neurodegenerative disease and iii/diagnostic groups. Associations between core CSF biomarkers and plasma NfL were determined. Results: Participants (N = 558, mean age = 69.2 ± 8.8, 56.5% women) were diagnosed with AD (n = 274, considering dementia and MCI stages), frontotemporal dementia (FTD, n = 55), Lewy body disease (LBD, n = 40, considering MCI and dementia stages), other neurodegenerative diseases, n = 57 (e.g Supranuclear Palsy, Corticobasal syndrome), non-neurodegenerative cognitive impairment (NND, n = 79, e.g. vascular lesions, epilepsy or psychiatric disorders) or subjective cognitive impairment (SCI, n = 53). Mean plasma NfL (log, pg/mL) levels were higher in neurodegenerative than non-neurodegenerative disorders (1.35 ± 0.2 vs 1.16 ± 0.23, p < 0.001), higher in all diagnostic groups than in SCI (1.06 ± 0.23) p < 0.001), and associated with the stage of cognitive impairment (p < 0.001). The addition of plasma NfL to a clinical model (age, MMSE and APOE ε4 carriership) marginally improved the discrimination of degenerative from non-degenerative disorders in ROC analysis (AUC clinical model: 0.81, 95% CI = [0.77;0.85] AUC clinical model + plasma NfL: AUC = 0.83 95% CI = [0.78;0.87], delta Akaike information criterion = −11.7). Discussion: Plasma NfL could help discrimination between degenerative and non-degenerative cognitive disorders, albeit not better than comprehensive clinical evaluation

Very massive star winds as sources of the short-lived radioactive isotope

Context. The 26Al short-lived radioactive nuclide is the source of the observed galactic diffuse γ-ray emission at 1.8 MeV. While different sources of 26Al have been explored, such as asymptotic giant branch stars, massive stellar winds, and supernovae, the contribution of very massive stars has not been studied so far. Aims. We study the contribution of the stellar wind of very massive stars, here, stars with initial masses between 150 and 300 M⊙, to the enrichment in 26Al of the galactic interstellar medium. Methods. We studied the production of 26Al by studying rotating and non-rotating very massive stellar models with initial masses between 150 and 300 M⊙ for metallicities Z = 0.006, 0.014, and 0.020. We compared this result to a simple Milky Way model and took the metallicity and the star formation rate gradients into account. Results. We obtain that very massive stars in the Z = 0.006 − 0.020 metallicity range might be very significant contributors to the 26Al enrichment of the interstellar medium. Typically, the contribution of the winds of massive stars to the total quantity of 26Al in the Galaxy increases by 150% when very massive stars are considered. Conclusions. Despite their rarity, very massive stars might be important contributors to 26Al and might overall be very important actors for nucleosynthesis in the Galaxy

Sur la systématique de Phlebotomus betisi et de deux nouvelles espèces apparentées du Laos avecproposition du nouveau sous-genre Lewisiu

International audiencePhlebotomus betisi was described from Malaysia and classified after its description in the subgenus Larroussius . It was the only species to have a pharyngeal armature composed of dot-like teeth and an annealed spermatheca whose head is carried by a neck in females. Males were characterized by having a style bearing five spines and a simple paramere. The study of sandflies originating from a cave in Laos enabled us to discover and describe two sympatric species close to Ph. betisi Lewis & Wharton, 1963 and new for Science: Ph. breyi Vongphayloth & Depaquit n. sp., and Ph. sinxayarami Vongphayloth & Depaquit n. sp. They were characterized morphologically, morphometrically, geomorphometrically, molecularly, and proteomically (MALDI-TOF). All approaches converged to validate the individualization of these species whose morphological differential characters lay in the two genders by the observation of the interocular suture and by the length of the last two segments of the maxillary palps. In males, the length of the genital filaments discriminates these species. Females are distinguished by the length of the ducts of the spermathecae as well as by the narrow or enlarged shape of the neck bearing their head. Lastly, the particular position of the spines of the gonostyle coupled with molecular phylogeny led us to remove these three species from the subgenus Larroussius Nizulescu, 1931 and to classify them in a new subgenus: Lewisius Depaquit & Vongphayloth n. subg.Phlebotomus betisi a été décrit de Malaisie et fut classé après sa description dans le sous-genre Larroussius . C’était la seule espèce à posséder chez la femelle une armature pharyngienne composée de dents en forme de points et à avoir une spermathèque annelée dont la tête est portée par un cou. Les mâles se caractérisaient par un style porteur de cinq épines et par un paramère simple. L’étude de Phlébotomes originaires d’une grotte du Laos nous a permis de découvrir et de décrire deux espèces sympatriques proches de Ph. betisi Lewis & Wharton, 1963 et nouvelles pour la Science : Ph. breyi Vongphayloth & Depaquit n. sp., et Ph. sinxayarami Vongphayloth & Depaquit n. sp. Elles ont été caractérisées morphologiquement, morphométriquement, géomorphométriquement, moléculairement et protéomiquement (MALDI-TOF). Toutes ces approches convergent pour valider l’individualisation de chacune de ces espèces dont les caractères morphologiques différentiels reposent dans les deux sexes par l’observation de la suture interoculaire et par la longueur des deux derniers segments des palpes maxillaires. Chez les mâles, la longueur des filaments génitaux discrimine ces espèces. Les femelles sont distinguées par la longueur des conduits des spermathèques ainsi que par la forme étroite ou élargie du cou portant la tête de ces spermathèques. Enfin, la position particulière des épines sur le gonostyle couplée à une phylogénie moléculaire nous amène à extraire ces trois espèces du sous genre Larroussius Nitzulescu, 1931 pour les classer dans un nouveau sous-genre : Lewisius Depaquit & Vongphayloth n. subg

Consultation « santé sexuelle et affective » : quelles attentes pour les personnes vivant avec le VIH ?

International audienceObjectivesPeople living with HIV (PLWH) are particularly affected in their sexual life. Medical support of PLWH's sexuality is increasingly proposed however no data are available. We assessed the interest of PLWH for sexual and emotional health support within a French HIV outpatient care facility.Population and methodsAnonymous questionnaire proposed to PVWH attending our facility. Five types of consultations were investigated: overall sexual and emotional health; HIV transmission and prevention; sexually transmitted diseases; sexual practices; recreational drugs. Cluster analysis in order to identify groups of PLWH with similar expectations.ResultsA total of 138 questionnaires completed: 64.5% were interested by at least one type of consultation. No significant differences between clusters by gender, age, or sexual orientation.ConclusionThese results confirm patients’ demand for sexual and emotional health support in the frame of PLWH's health care. Patients declaring no interest for this type of consultation were no different from those interested.ObjectifsLes personnes vivant avec le VIH (PVVIH) sont particulièrement affectées dans leur vie sexuelle. La prise en charge médicale de leur sexualité se développe, mais aucune donnée n’est disponible. Évaluation de l’intérêt pour des consultations de santé sexuelle et affective au sein d’une unité ambulatoire de prise en charge des PVVIH.Patients et méthodesQuestionnaire anonyme proposé aux patients fréquentant le service. Cinq types de consultations évaluées : santé sexuelle et affective, modes de transmission et de prévention, infections sexuellement transmissibles, pratiques sexuelles, drogues récréatives. Analyse de cluster pour identifier des patients ayant des besoins similaires.RésultatsAu total, 138 questionnaires complétés. Le pourcentage des intéressés par au moins un type de consultation est de 64,5. Pas de différence en termes d’âge, de sexe ou d’orientation sexuelle entre les clusters.ConclusionCette étude met en évidence le besoin des patients concernant la prise en charge de leur santé sexuelle et affective

On the systematics of

Phlebotomus betisi was described from Malaysia and classified after its description in the subgenus Larroussius. It was the only species to have a pharyngeal armature composed of dot-like teeth and an annealed spermatheca whose head is carried by a neck in females. Males were characterized by having a style bearing five spines and a simple paramere. The study of sandflies originating from a cave in Laos enabled us to discover and describe two sympatric species close to Ph. betisi Lewis & Wharton, 1963 and new for Science: Ph. breyi Vongphayloth & Depaquit n. sp., and Ph. sinxayarami Vongphayloth & Depaquit n. sp. They were characterized morphologically, morphometrically, geomorphometrically, molecularly, and proteomically (MALDI-TOF). All approaches converged to validate the individualization of these species whose morphological differential characters lay in the two genders by the observation of the interocular suture and by the length of the last two segments of the maxillary palps. In males, the length of the genital filaments discriminates these species. Females are distinguished by the length of the ducts of the spermathecae as well as by the narrow or enlarged shape of the neck bearing their head. Lastly, the particular position of the spines of the gonostyle coupled with molecular phylogeny led us to remove these three species from the subgenus Larroussius Nizulescu, 1931 and to classify them in a new subgenus: Lewisius Depaquit & Vongphayloth n. subg