Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure

Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA) in rats requires a long feeding period (6 months), although a docosahexaenoic (DHA) acid-supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n-3 polyunsaturated fatty acid (PUFA) composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL), mitochondrial (MI), nuclear (NU) and sarcoplasmic reticulum (SR) membrane fractions. Male Wistar rats were randomly assigned to 3 dietary groups (n = 10/diet/period), either n-3 PUFA-free diet (CTL), or ALA or DHA-rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC) after lipid extraction. As expected the n-3 PUFA-rich diets incorporated n-3 PUFA instead of n-6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n-3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n-3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA). N-3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing. With the ALA diet the n-3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response

DNA Polymerase η Is Involved in Hypermutation Occurring during Immunoglobulin Class Switch Recombination

Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR). These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase η (pol η), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol η is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes

Sociétés, État, populations en Russie et en URSS

Alain Blum, directeur d’études Formation et action de l’État, société et population en Russie et en URSS (XIXe-XXe siècles) Nous avons poursuivi cette année la réflexion engagée l’année précédente portant sur les pratiques administratives d’un État autoritaire, l’URSS, en travaillant essentiellement sur la genèse de ces pratiques, entre 1917 et 1939. Mettre l’accent sur cet aspect, et cette période, nous a en effet permis de fonder notre démarche sur une analyse précise des interactions entre..

Use of the 3D radon transform to examine the properties of oceanic Rossby waves

One of the most successful applications of satellite-borne radar altimeter data over the oceans in recent years has been the extraction of information about long-wavelength baroclinic Rossby (or planetary) waves, which play a significant role in ocean circulation and climate dynamics. These waves cross ocean basins from east to west at speeds of few centimetres per second at mid-latitudes. The cross-basin propagation time may therefore be several months or even years and an accurate estimation of the speed of the waves is important. We review the methods for obtaining information on Rossby wave velocity from altimetry data, particularly the two-dimensional Radon transform. Unfortunately the use of longitude-time plots, although it allows the estimation of the zonal phase speeds, does not give any information on the speed vector when the propagation of the waves is not purely zonal (east-west). We show how the two-dimensional Radon Transform can be generalised to three dimensions, enabling not only the true propagation velocity component to be determined, but also the direction of the waves and thus any deviation from the pure-westward case. As examples of the application of this extended technique, we show maps of direction, speed and energy of Rossby waves in the North Atlantic Ocean

Sociétés, État, populations en Russie et en URSS

Alain Blum, directeur d’études Formation de l’État et société en Russie et en URSS, XIXe-XXe siècles Ce séminaire visait tant à étudier, en partant de l’administration statistique soviétique, la formation de l’État soviétique et des formes de gouvernement, qu’à approfondir la question de l’usage des sources d’archives soviétiques. La formation de l’État a été étudiée en suivant une démarche prosopographique, qui permettait de recouper des sources diverses, que ce soit témoignages, biographies..

Sociétés, État, populations en Russie et en URSS

Alain Blum, directeur d’études Formation et action de l’État, société et population en Russie et en URSS (XIXe-XXe siècles) Nous avons poursuivi cette année la réflexion engagée l’année précédente portant sur les pratiques administratives d’un État autoritaire, l’URSS, en travaillant essentiellement sur la genèse de ces pratiques, entre 1917 et 1939. Mettre l’accent sur cet aspect, et cette période, nous a en effet permis de fonder notre démarche sur une analyse précise des interactions entre..

A modified self‐controlled case series method for event‐dependent exposures and high event‐related mortality, with application to COVID‐19 vaccine safety

We propose a modified self‐controlled case series (SCCS) method to handle both event‐dependent exposures and high event‐related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID‐19 vaccines. Event‐dependence of vaccinations, and high event‐related mortality, are likely to arise in other SCCS studies of COVID‐19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death

Non-contrast CT markers of intracerebral hematoma expansion : a reliability study

Objectives: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion. Methods: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter and intra-rater agreement were measured using Gwet’s AC1, with a coefficient > 0.60 indicating substantial to almost perfect agreement. Results: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters’ experience, hematoma location, volume or anticoagulation status. Intrarater agreement was substantial to almost perfect for all but the black hole marker. Conclusion: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement