Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.</p

The synthesis and spectroscopic characterisation of hydrotalcite formed from aluminate solutions

Raman spectroscopy has been used to characterise nine hydrotalcites prepared from aluminate and magnesium solutions (magnesium chloride and seawater). The aluminate hydrotalcites are proposed to have the following formula Mg6Al2(OH)16(CO32-).xH2O, Mg6Al2(OH)16(CO32-,SO42-).xH2O, and Mg6Al2(OH)16(SO42-).xH2O. The synthesis of these hydrotalcites using seawater results in the intercalation of sulfate anions into the hydrotalcite interlayer. The spectra have been used to assess the molecular assembly of the cations and anions in the hydrotalcite structures. The spectra have been conveniently subdivided into spectral features based upon the carbonate anion, the hydroxyl units and water units. This investigation has shown the ideal conditions to form hydrotalcite from aluminate solutions is at pH 14 using magnesium chloride. Changes in synthesis conditions resulted in the formation of impurity products aragonite, thenardite, and gypsum

Synthesis and thermal stability of hydrotalcites containing manganese

The hydrotalcite based upon manganese known as charmarite Mn4Al2(OH)12CO3•3H2O has been synthesised with different Mn/Al ratios from 4:1 to 2:1. Impurities of manganese oxide, rhodochrosite and bayerite at low concentrations were also produced during the synthesis. The thermal stability of charmarite was investigated using thermogravimetry. The manganese hydrotalcite decomposed in stages with mass loss steps at 211, 305 and 793°C. The product of the thermal decomposition was amorphous material mixed with manganese oxide. A comparison is made with the thermal decomposition of the Mg/Al hydrotalcite. It is concluded that the synthetic charmarite is slightly less stable than hydrotalcite

Raman spectroscopy of gallium- and zinc-based hydrotalcites

Insight into the unique structure of hydrotalcites (HTs) has been obtained using Raman spectroscopy. Gallium-contg. HTs of formula Zn4 Ga2(CO3)(OH)12 · xH2O (2:1 ZnGa-HT), Zn6 Ga2(CO3)(OH)16 · xH2O (3:1 ZnGa-HT) and Zn8 Ga2(CO3)(OH)18 · xH2O (4:1 ZnGa-HT) have been successfully synthesized and characterised by X-ray diffraction (XRD) and Raman spectroscopy. The d(003) spacing varies from 7.62 Å for the 2:1 ZnGa-HT to 7.64 Å for the 3:1 ZnGa-HT. The 4:1 ZnGa-HT showed a decrease in the d(003) spacing, compared to the 2:1 and 3:1 compds. Raman spectroscopy complemented with selected IR data has been used to characterize the synthesized gallium-contg. HTs. Raman bands obsd. at around 1050, 1060 and 1067 cm-1 are attributed to the sym. stretching modes of the (CO32-) units. Multiple ν3 (CO32-) antisym. stretching modes are found between 1350 and 1520 cm-1, confirming multiple carbonate species in the HT structure. The splitting of this mode indicates that the carbonate anion is in a perturbed state. Raman bands obsd. at 710 and 717 cm-1 and assigned to the ν4 (CO32-) modes support the concept of multiple carbonate species in the interlayer

Post-mortem storage conditions and cooking methods affect long-chain omega-3 fatty acid content in Atlantic mackerel (Scomber scombrus)

International audienceLong-chain omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are health beneficial lipids found in high concentration in pelagic fishes, including Atlantic mackerel. While EPA and DHA are sensitive to oxidative degradation during fish storage and processing, post-mortem degradation in the first hours following fish death is poorly documented. In this study, we stored fish at two temperatures (2-4°C and 18-20°C) and monitored EPA+DHA content in dorsal fillet 6, 12 and 24 hours after fish death and after cooking (grill or steam). Storage duration was the most influencing factor, and EPA+DHA loss was faster at 18-20°C. Six hours after fish death, and regardless of storage temperature EPA+DHA content decreased by 1.3±1.3 mg.g-1 (9.6±9.5% of the initial content). EPA+DHA losses were highly variable among individuals, probably because of other sources of variability (e.g., sampling position). Handling between fishing operation and deep-frozen storage should be as short and as cool as possible to preserve EPA+DHA and for food safety. Regarding cooking, both EPA+DHA and mono-unsaturated fatty acids increased in grilled fillets

Herculanum. Conception du modèle 3D de restitution et restauration virtuelle de la Casa di Nettuno ed Anfitrite

National audienc

Loss of reactivity of vaccine-induced CD4 T cells in immunized monkeys after SIV/HIV challenge.

International audienceBACKGROUND: Immunization protocols involving priming with DNA and boosting with recombinant live virus vectors such as recombinant modified Vaccinia Ankara (rMVA) are considered as vaccine candidates against HIV. Such protocols improve the outcome of simian/human immunodeficiency virus (SHIV) pathogenic challenge in Rhesus monkeys. OBJECTIVES: To investigate the fate of vaccine-induced T cells after a mucosal SHIV challenge. METHODS: We immunized Rhesus monkeys (Macaca mulatta) by DNA priming followed by rMVA boost. After intrarectal challenge with SHIV 89.6P, immunized animals demonstrated early control of viral replication and stable CD4 T-cell counts. We monitored T-cell responses by measuring IFN-gamma secretion and proliferation. RESULTS: Immunization induced strong and sustained SHIV-specific CD4 and CD8 T-cell responses. CD8 T-cell responses were recalled during acute infection, whereas none of the vaccine-induced SHIV-specific CD4 T-cell responses were recalled. Moreover, most of the CD4 T-cell responses became undetectable in peripheral blood or lymph nodes even after in-vitro peptide stimulation. In contrast, we persistently detected CD4 T-cell responses specific for control recall antigens in infected animals. CONCLUSION: SHIV 89.6P challenge results in a lack of reactivity of vaccine-induced SHIV-specific CD4 T cells. These results may have important implications in the AIDS vaccine field, especially for the evaluation of new vaccine candidates, both in preventive and therapeutic trials

Red muscle of small pelagic fishes? fillets are high-quality sources of essential fatty acids

International audienceSmall pelagic fishes such as sardine and anchovy are among the richest species in essential fatty acids that are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), whose bioavailability may depend on its esterification to polar or neutral lipids. The EPA and DHA quantities in neutral and polar lipids were compared in sardine (from the English Channel) and anchovy (from the Bay of Biscay) fillets, and in red and white muscle separately. Sardine fillets had the highest EPA+DHA content (760 ± 670 vs 370 ± 510 mg/100 g in anchovy fillets), mainly because of their largest proportion of lipid-rich red muscle and its relatively high lipid content. However, DHA esterified to polar lipids was higher in anchovy than in sardine fillet (270 ± 60 vs 230 ± 30 mg/100 g). EPA+DHA content were higher in red than white muscle for both species. This study highlights the nutritional interest of red muscle to provide essential dietary fatty acids to consumers, and the necessity to consider its importance in nutrition studies

Red muscle of small pelagic fishes’ fillets are high-quality sources of essential fatty acids

Small pelagic fishes such as sardine and anchovy are among the richest species in essential fatty acids that are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), whose bioavailability may depend on its esterification to polar or neutral lipids. The EPA and DHA quantities in neutral and polar lipids were compared in sardine (from the English Channel) and anchovy (from the Bay of Biscay) fillets, and in red and white muscle separately. Sardine fillets had the highest EPA+DHA content (760±670 vs 370±510 mg/100 g in anchovy fillets), mainly because of their largest proportion of lipid-rich red muscle and its relatively high lipid content. However, DHA esterified to polar lipids was higher in anchovy than in sardine fillet (270±60 vs 230±30 mg/100 g). EPA+DHA content were higher in red than white muscle for both species. This study highlights the nutritional interest of red muscle to provide essential dietary fatty acids to consumers, and the necessity to consider its importance in nutrition studies