Design and synthesis of metabolically stable atrial natriuretic factor analogs. Amino- and carboxy-terminal stabilization

Two analogs of rat atrial natriuretic factor, rANF7-28-NH2 and [Mpr7,Ala20,D-Arg27]rANF7-27-NH2, were prepared by the solid-phase method. These peptides had 2-fold and 7-fold less affinity, respectively, than rANF1-28 in binding to membranes prepared from cultured aortic smooth muscle cells, and both peptides were 5-fold less potent than rANF1-28 in relaxing serotonin-contracted rabbit aortic rings. rANF7-28-NH2 was rapidly degraded by rat kidney homogenates but [Mpr7,Ala20,D-Arg27]rANF7-27-NH2 had enhanced stability against rat kidney homogenate degradation. However, this in vitro stability did not translate into an extended duration of action in vivo.     

Establishment of the predator Laricobius nigrinus,introduced as a biological control agent for hemlock woolly adelgid in Virginia,USA

BioControl - Laricobius nigrinus Fender (Coleoptera: Derodontidae), a predatory beetle native to western North America, has been released since 2003 for management of hemlock woolly adelgid (HWA),...     

Invasive plants negatively impact native,but not exotic,animals

Despite our growing understanding of the impacts of invasive plants on ecosystem structure and function, important gaps remain, including whether native and exotic species respond differently to plant invasion. This would elucidate basic ecological interactions and inform management. We performed a meta‐analytic review of the effects of invasive plants on native and exotic resident animals. We found that invasive plants reduced the abundance of native, but not exotic, animals. This varied by animal phyla, with invasive plants reducing the abundance of native annelids and chordates, but not mollusks or arthropods. We found dissimilar impacts among “wet” and “dry” ecosystems, but not among animal trophic levels. Additionally, the impact of invasive plants increased over time, but this did not vary with animal nativity. Our review found that no studies considered resident nativity differences, and most did not identify animals to species. We call for more rigorous studies of invaded community impacts across taxa, and most importantly, explicit consideration of resident biogeographic origin. We provide an important first insight into how native and exotic species respond differently to invasion, the consequences of which may facilitate cascading trophic disruptions further exacerbating global change consequences to ecosystem structure and function.     

Cell recovery comparison between plasma depletion/reduction- and red cell reduction-processing of umbilical cord blood

Background aimsLimited cell dose has hampered the use of cord blood transplantation (CBT) in adults. One method of minimizing nucleated cell loss in cord blood (CB) processing is to deplete or reduce plasma but not red blood cells - plasma depletion/reduction (PDR).MethodsThe nucleated cell loss of PDR was studied, and determined to be less than 0.1% in the discarded supernatant plasma fraction in validation experiments. After testing and archival sampling, the median nucleated cell recovery for PDR processing was 90%, and median CD34⁺ cell recovery 88%. In a CB bank inventory of 12 339 products with both pre- and post-processing total nucleated cells (TNC), PDR processing resulted in median post-processing TNC recoveries of 90.0% after testing and archival samples removal. Using the same 10 CB units divided into two halves, we compared directly the recovery of PDR against hydroxyethyl starch red cell reduction (RCR) for TNC, CD34⁺ cells and colony-forming units (CFU-GM, CFU-E, CFU-GEMM and total CFU) after parallel processing. We also compared the loss of very small embryonic-like stem cells (VSEL).ResultsWe demonstrated significantly higher recoveries using PDR for TNC (124%), CD34⁺ cells (121%), CFU-GM (225%), CFU-GEMM (201%), total CFU (186%) and VSEL (187%). The proportion of high TNC products was compared between 10 912 PDR and 38 819 RCR CB products and found to be 200% higher for products that had TNC ≥150 × 10⁷ (P = 0.0001) for the PDR inventory.ConclusionsOur data indicate that PDR processing of CB provides a significantly more efficient usage of this valuable and scarce resource.     

Pharmacological profile of 8-amino octanoic acid substituted atrial natriuretic factor analogs

A series of six analogs of rat atrial natriuretic factor have been prepared by the solid-phase method. The modified analogs contain 8-amino octanoic acid (a simple alkyl spacer) in place of selected tripeptides. Binding affinity to cultured aortic smooth muscle cell membranes suggests that the sequence Arg11-Gly16 is important for binding. Vasorelaxant activity on serotonin contracted rabbit aortic rings indicates that the Phe8-Gly16 sequence must be present for vasorelaxation. In anesthetized rats, the natriuretic and diuretic effects of an IV bolus dose correlate with in vitro vasodilatory activity. The alkyl spacer approach provides a facile method to quickly determine key regions of a large peptide involved in molecular recognition.     

Synthesis and activity of partial retro-inverso modified atrial natriuretic factor analogs

The synthesis and pharmacological activity of partial retro-inverso modified rat atrial natriuretic factor (rANF) analogs is described. The route to these compounds utilized a combination of solution and solid-phase methods. The analogs prepared all contain a reversed amide bond (psi[NHCO]) at the Ser 25 to Phe26 linkage. This bond has been suggested to play a key role in the metabolic inactivation of ANF. The analogs are of comparable potency to the endogenous peptide rANF1-28 in binding to cultured rat vascular smooth muscle cells, in relaxing serotonin contracted rabbit aortic rings, and as natriuretic/diuretic agents in anesthetized rats. None of the peptides has an extended duration of action in vivo.