936-86 Plasma Fibrinogen Level Predicts Severity of Intimal Thickening After Cardiac Transplantation

Diffuse atherosclerosis is the primary reason for late graft failure after cardiac transplantation. Because there is increasing evidence that imbalances in the hemostatic and fibrinolytic pathways are associated with allogeneic rejection, we hypothesized that atherothrombotic risk factors may contribute to accelerated atherosclerosis. We therefore prospectively evaluated the burden of coronary atherosclerosis by intravascular ultrasound (IVUS) in 20 patients and measured plasma fibrinogen (FGN). lipoprotein (a) (Lp(a)) and net fibrinolytic activity of plasma using a standard fibrin plate assay. Intimal thickening was quantified using IVUS by measuring the intimal index (li=intimal area/[intimal area+luminal area]) in 2–5 segments of the LAD using planimetry. The maximal Ii per patient was calculated and indexed to the time post-transplant (Mxli/Yr). FGN predicted severity of Mxli/Yr (r2=0.41, p=0.008). In patients with decreased plasma fibrinolytic activity (lytic zone <100 mm2). Mxli/Yr was increased ten-fold (0.21±0.17 vs. 0.02±0.02, p=0.002). Because Lp(a) colocalizes with fibrinogen in the vessel wall and inhibits fibrinolysis, we correlated plasma Lp(a) levels with the degree of intimal thickening. Lp(a) did not predict Mxli/Yr (p=NS). In conclusion, these data suggest that plasma FGN and net fibrinolytic activity predict the degree of intimal thickening and that fibrin deposition may play an integral role in diffuse coronary atherosclerosis after cardiac transplantation

Attenuation of coronary vascular resistance by selective alpha1,-adrenergic blockade in patients with coronary artery disease

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phen-tolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 ± 5 beats/min (± 1SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 ± 4% (102 ± 14 to 111 ± 14 mm Hg, p < 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 ± 19% (1.02 ± 0.46 to 1.15 ± 0.57 units, p < 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 ± 5% (p < 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 ± 11%, p = NS), which was significantly less than before trimazosin (p < 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha1-receptor blockade.These data suggest that although the hypertensive response to cold pressor testing is somewhat blunted by selective alpha1,-adrenoceptor blockade, the reflex coronary vasoconstriction during adrenergic stimulation in some patients with coronary artery disease can be significantly attenuated. Use of agents that block alpha2-adrenoceptors has been clinically unsatisfactory because of the adverse myocardial effects of increased norepinephrine release. Selective alpha1-receptor blockade may have an additional advantage over nonselective alpha-adrenergic blockade in that the release of norepinephrine is also attenuated, thus potentially producing less augmentation of heart rate and myocardial oxygen demand

Phosphate concentration and arbuscular mycorrhizal colonisation influence the growth, yield and expression of twelve PHT1 family phosphate transporters in foxtail millet (Setaria italica)

Phosphorus (P) is an essential element which plays several key roles in all living organisms. Setaria italica (foxtail millet) is a model species for panacoid grasses including several millet species widely grown in arid regions of Asia and Africa, and for the bioenergy crop switchgrass. The growth responses of S. italica to different levels of inorganic phosphate (Pi) and to colonisation with the arbuscular mycorrhizal fungus Funneliformis mosseae (syn. Glomus mosseae) were studied. Phosphate is taken up from the environment by the PHT1 family of plant phosphate transporters, which have been well characterized in several plant species. Bioinformatic analysis identified 12 members of the PHT1 gene family (SiPHT1;1-1;12) in S. italica, and RT and qPCR analysis showed that most of these transporters displayed specific expression patterns with respect to tissue, phosphate status and arbuscular mycorrhizal colonisation. SiPHT1;2 was found to be expressed in all tissues and in all growth conditions tested. In contrast, expression of SiPHT1;4 was induced in roots after 15 days growth in hydroponic medium of low Pi concentration. Expression of SiPHT1;8 and SiPHT1;9 in roots was selectively induced by colonisation with F. mosseae. SiPHT1;3 and SiPHT1;4 were found to be predominantly expressed in leaf and root tissues respectively. Several other transporters were expressed in shoots and leaves during growth in low Pi concentrations. This study will form the basis for the further characterization of these transporters, with the long term goal of improving the phosphate use efficiency of foxtail millet

Dense sampling of bird diversity increases power of comparative genomics (vol 587, pg 252, 2020)

Publishe

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development