Amyloid burden and white matter hyperintensities mediate age-related cognitive differences

This study examined the additive versus synergistic contribution of beta-amyloid (Aβ) and white matter hyperintensities (WMHs) across 7 cognitive domains in 104 cognitively normal older adults. It also measured the extent to which age-related differences in cognition are driven by measurable brain pathology. All participants underwent neuropsychological assessment along with magnetic resonance imaging and Pittsburg compound B-positron emission tomography imaging for Aβ quantification. WMH severity was quantified using the age-related white matter changes scale. Stepwise regressions, moderation, and mediation modeling were performed. Our findings show that Aβ deposition single-handedly predicts poorer episodic memory performance and that Aβ and WMHs contribute additively to poorer performance in working memory and language while carrying synergistic associations with executive functions and attention. Through mediation modeling, we demonstrated that the influence of age over episodic memory, working memory, executive functions, and language is fully mediated by brain pathology. This study permits to conclude that, in healthy older adults, (1) Aβ burden and WMHs have synergistic associations with some cognitive domains and (2) age-related differences in most cognitive domains are driven by brain pathology associated with dementia

Education as a moderator of the relationship between episodic memory and amyloid load in normal aging

The current study explored whether education, a proxy of cognitive reserve, modifies the association between episodic memory (EM) performance and βeta-amyloid load (Aβ), a biomarker of Alzheimer’s disease, in a cohort of cognitively normal older adults. One hundred and four participants (mean age 73.3 years) evenly spread out in three bands of education were recruited. Participants underwent neuropsychological assessment, structural MRI as well as PET imaging to quantify Aβ load. Moderation analyses and the Johnson–Neyman technique were carried out to examine the interaction of education with Aβ load to predict EM performance. Linear regressions were then performed within each group of education to better illustrate the interaction effect (all analyses were controlled for age and sex). The interaction between education and Aβ load was significant (p < .05) for years of education, reaching a cutoff point of 13.5 years, above which the relationship between Aβ load and EM was no longer significant. Similarly, significant associations were found between Aβ and EM among participants with secondary (p < .01) and preuniversity education (p < .01), but not with a university degree (p = .253). EM performance is associated with Aβ load in cognitively normal older individuals, and this relationship is moderated by educational attainment

Estudio técnico de las pinturas murales de Germolles: la contribución de las técnicas de imagen

[EN] The Château de Germolles is one of the rare palace in France dating from the 14th century. The noble floor is decorated with wall paintings that are a unique example of courtly love spirit that infused the princely courts of the time. After being concealed sometime in the 19th century, the paintings were rediscovered and uncovered in the middle of the 20th century and partly restored at the end of the 1990s. No scientific documentation accompanied these interventions and important questions, such as the level of authenticity of the mural decorations and the original painting technique(s) used in the medieval times remained unanswered. The combined scientific and financial supports of COSCH Cost Action and DRAC-Burgundy enabled to study Germolles’ wall paintings using some of the most innovative imaging and analytical techniques and to address some of the questions raised. The study provided significant information on the material used in the medieval times and on the conservation condition of the paintings. The data collected is vast and varied and exposed the owners of the property to the challenges of data management.[ES] El castillo de Germolles es uno de los raros palacios principescos en Francia que data del siglo XIV. La planta noble está decorada con pinturas murales que son un ejemplo único del amor cortés, ese espíritu que se divulgó en las cortes de la época.Ocultadas desde el fin del siglo XIX, las pinturas fueron descubiertas en la mitad del siglo XXy fueron parcialmente restauradas al finalde la década de 1990. No hay documentación científica queacompañelas intervenciones, y cuestiones importantesse quedaronsin repuesta, en particular el nivel de autenticidad de las decoraciones de las paredes, así como lastécnicaspictóricasutilizadasen laépoca medieval. El apoyo científico y económico de la Acción Cost COSCH y de la DRAC de Borgoña permitió elestudio delas pinturas murales de Germolles con algunas de las técnicas de imagen y analíticasmás innovadoras, con tal de responder a algunas de las cuestiones planteadas. El estudio proporcionó informaciónrelevante en lo que se refiere al material utilizado durante la Edad Mediay sobreel estado de conservación de las pinturas. La toma de datos es ampliay variada, y expuso a los dueños de la propiedad al desafío de la gestión de datos.This project would not have been possible without the financial support by DRAC-Burgundy and the COST Action TD1201: Colour and Space in Cultural Heritage (COSCH) (www.cosch.info) which the authors wish to sincerely thank.Degrigny, C.; Piqué, F.; Papiashvili, N.; Guery, J.; Mansouri, A.; Le Goïc, G.; Detalle, V.... (2016). Technical study of Germolles’ wall paintings: the input of imaging technique. Virtual Archaeology Review. 7(15):1-8. https://doi.org/10.4995/var.2016.5831SWORD18715Giovannoni, S., Matteini, M., & Moles, A. (1990). Studies and developments concerning the problem of altered lead pigments in wall painting. Studies in Conservation, 35(1), 21-25. doi:10.1179/sic.1990.35.1.21Manuel, A., Gattet, E., De Luca, L., & Veron, P. (2013). An approach for precise 2D/3D semantic annotation of spatially-oriented images for in situ visualization applications. 2013 Digital Heritage International Congress (DigitalHeritage). doi:10.1109/digitalheritage.2013.6743752Wefers, S., Reich, T., Tietz, B. and Boochs, F. 2016. SIVT – Processing, Viewing, and Analysis of 3D Scans of the Porthole Slab and Slab B2 of Züschen I. In: S. Campana, R. Sopigno, G. Carpentiero and M. Cirillo, eds, CAA2015. Keep the Revolution Going. Proceedings of the 43rd Annual Conference on Computer Applications and Quantitative Methods In Archaeology. Oxford : Archaeopress Publishing Ltd, pp. 1067-1080

E2F6 initiates stable epigenetic silencing of germline genes during embryonic development.

In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

A global database of water vapor isotopes measured with high temporal resolution infrared laser spectroscopy

The isotopic composition of water vapour provides integrated perspectives on the hydrological histories of air masses and has been widely used for tracing physical processes in hydrological and climatic studies. Over the last two decades, the infrared laser spectroscopy technique has been used to measure the isotopic composition of water vapour near the Earth's surface. Here, we have assembled a global database of high temporal resolution stable water vapour isotope ratios (delta O-18 and delta D) observed using this measurement technique. As of March 2018, the database includes data collected at 35 sites in 15 Koppen climate zones from the years 2004 to 2017. The key variables in each dataset are hourly values of delta O-18 and delta D in atmospheric water vapour. To support interpretation of the isotopologue data, synchronized time series of standard meteorological variables from in situ observations and ERA5 reanalyses are also provided. This database is intended to serve as a centralized platform allowing researchers to share their vapour isotope datasets, thus facilitating investigations that transcend disciplinary and geographic boundaries