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Vitamin K antagonists (VKA) and non-vitamin K oral antagonist anticoagulants (NOAC) are used in the clinic to reduce risk of thrombosis. However, they also exhibit vascular off-target effects. The aim of this study is to compare VKA and NOAC on atherosclerosis progression and calcification in an experimental setup.
Female Apoe
mice (age 12weeks) were fed Western-type diet as control or supplemented with dabigatran etexilate or warfarin for 6 or 18weeks. Vascular calcification was measured in whole aortic arches using µCT and [
F]-NaF. Atherosclerotic burden was assessed by (immuno)histochemistry. Additionally, in vitro effects of warfarin, thrombin, and dabigatran on primary vascular smooth muscle cells (VSMC) were assessed.
Short-term treatment with warfarin promoted formation of atherosclerotic lesions with a pro-inflammatory phenotype, and more rapid plaque progression compared with control and dabigatran. In contrast, dabigatran significantly reduced plaque progression compared with control. Lon vascular side effects and reveals beneficial effects on atherosclerosis progression and calcification. The choice of anticoagulation impacts atherosclerotic disease by differential off target effect. Future clinical studies should test whether this beneficial effect also applies to patients.Controlling the reactivity of carbene intermediates is a key parameter in the development of selective carbene transfer reactions and is usually achieved by metal complexes via singlet metal-carbene intermediates. In this combined experimental and computational studies, we show that the reactivity of free diaryl carbenes can be controlled by the electronic properties of the substituents without the need of external additives. The introduction of electron-donating and -withdrawing groups results in a significant perturbation of singlet triplet energy splitting of the diaryl carbene intermediate and of activation energies of consecutive carbene transfer reactions. This strategy now overcomes a long-standing paradigm in the reactivity of diaryl carbenes and allows the realization of highly chemoselective carbene transfer reactions with alkynes. We could show that free diaryl carbenes can be readily accessed via photolysis of the corresponding diazo compounds and that these carbenes can undergo highly chemoselective cyclopropenation, cascade, or C-H functionalization reactions. Experimental and theoretical mechanistic analyses confirm the participation of different carbene spin states and rationalize for the observed reactivity.Institutional care has been shown to increase the risk of attention problems in children, but some children are more sensitive to their environment, both for better and for worse. With this in mind, the current study examined the moderating role of temperament (falling reactivity) between early adversity and attention skills. Six- to 15-month-old infants residing in institutions (n = 63) and infants reared by their biological families from low socioeconomic environments (n = 59) were recruited. The infants' attention skills were measured by calculating the length of time they spent looking at toys. The infants' temperaments were measured by a subscale of the Infant Behavior Questionnaire (falling reactivity/rate of recovery from distress). The findings were in line with the differential susceptibility theory. Compared to infants with high levels of falling reactivity, infants with lower levels of falling reactivity had better attention skills if they were in a family group, but they had lower attention skills if they were residing in institutions. The attention skills of the infants who had higher scores for falling reactivity did not appear to be affected by the adverse environment.Obtaining high biomass yields of specific microorganisms for culture-independent approaches is a challenge faced by scientists studying organism's recalcitrant to laboratory conditions and culture. This difficulty is highly decreased when studying magnetotactic bacteria (MTB) since their unique behaviour allows their enrichment and purification from other microorganisms present in aquatic environments. Here, we use Lake Pavin, a permanently stratified lake in the French Massif Central, as a natural laboratory to optimize collection and concentration of MTB that thrive in the water column and sediments. A method is presented to separate MTB from highly abundant abiotic magnetic particles in the sediment of this crater lake. For the water column, different sampling approaches are compared such as in situ collection using a Niskin bottle and online pumping. By monitoring several physicochemical parameters of the water column, we identify the ecological niche where MTB live. Then, by focusing our sampling at the peak of MTB abundance, we show that the online pumping system is the most efficient for fast recovering of large volumes of water at a high spatial resolution, which is necessary considering the sharp physicochemical gradients observed in the water column. Taking advantage of aerotactic and magnetic MTB properties, we present an efficient method for MTB concentration from large volumes of water. Our methodology represents a first step for further multidisciplinary investigations of the diversity, metagenomic and ecology of MTB populations in Lake Pavin and elsewhere, as well as chemical and isotopic analyses of their magnetosomes.A deeper understanding of the complex relationship between plants and their microbiota is allowing researchers to appreciate a plethora of possibilities to improve crops using chemical-free alternatives based on beneficial microorganisms. An increase in crop yield from the promotion of plant growth or even simultaneous protection of the plants from the attack of phytopathogens can be achieved in the presence of different plant-associated microorganisms known as plant-growth-promoting rhizobacteria (PGPR) and biocontrol agents (BCAs), respectively. Thus, the study of the great diversity of plant-microbe and microbe-microbe interactions is an attention-grabbing topic covering studies of interactions since the plant seed and through all developmental stages, from root to shoot. The intricate communication systems that plant holobionts co-evolved has resulted in many different strategies and interplays between these organisms shaping the bacterial communities and the plant fitness simultaneously. Torkinib Herein, we emphasize two understudied delivery systems existing in plant-associated bacteria the type VI secretion system (T6SS) and the membrane vesicles with a huge potential to boost a highly demanded and necessary green agriculture.
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