Angiotensin-converting enzyme activity and inhibition in dogs with cardiac disease and an angiotensin-converting enzyme polymorphism

OBJECTIVE The objective of this study was to evaluate angiotensin-converting enzyme (ACE) activity in dogs and with and without an ACE polymorphism in the canine ACE gene, before and after treatment with an ACE inhibitor. METHODS Thirty-one dogs (20 wild-type, 11 ACE polymorphism) with heart disease were evaluated with ACE activity measurement and systolic blood pressure before and after administration of an ACE inhibitor (enalapril). RESULTS Median pre-treatment ACE activity was significantly lower for ACE polymorphism dogs than for dogs with the wild-type sequence ( P=0.007). After two weeks of an ACE inhibitor, ACE activity was significantly reduced for both genotypes (wild-type, P<0.0001; ACE polymorphism P=0.03); mean post-therapy ACE activity was no different between the groups. CONCLUSION An ACE polymorphism is associated with lower levels of ACE activity. Dogs with the polymorphism still experience suppression of ACE activity in response to an ACE inhibitor. It is possible that the genetic status and ACE activity of dogs may impact the response of dogs with this variant to an ACE inhibitor

The Effects of Herbivory by a Mega- and Mesoherbivore on Tree Recruitment in Sand Forest, South Africa

Herbivory by megaherbivores on woody vegetation in general is well documented; however studies focusing on the individual browsing effects of both mega- and mesoherbivore species on recruitment are scarce. We determined these effects for elephant Loxodonta africana and nyala Tragelaphus angasii in the critically endangered Sand Forest, which is restricted to east southern Africa, and is conserved mainly in small reserves with high herbivore densities. Replicated experimental treatments (400 m2) in a single forest patch were used to exclude elephant, or both elephant and nyala. In each treatment, all woody individuals were identified to species and number of stems, diameter and height were recorded. Results of changes after two years are presented. Individual tree and stem densities had increased in absence of nyala and elephant. Seedling recruitment (based on height and diameter) was inhibited by nyala, and by elephant and nyala in combination, thereby preventing recruitment into the sapling stage. Neither nyala or elephant significantly reduced sapling densities. Excluding both elephant and nyala in combination enhanced recruitment of woody species, as seedling densities increased, indicating that forest regeneration is impacted by both mega- and mesoherbivores. The Sand Forest tree community approached an inverse J-shaped curve, with the highest abundance in the smaller size classes. However, the larger characteristic tree species in particular, such as Newtonia hildebrandtii, were missing cohorts in the middle size classes. When setting management goals to conserve habitats of key importance, conservation management plans need to consider the total herbivore assemblage present and the resulting browsing effects on vegetation. Especially in Africa, where the broadest suite of megaherbivores still persists, and which is currently dealing with the ‘elephant problem’, the individual effects of different herbivore species on recruitment and dynamics of forests and woodlands are important issues which need conclusive answers

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Biodiversity recovery of Neotropical secondary forests

Old-growth tropical forests harbor an immense diversity of tree species but are rapidly being cleared, while secondary forests that regrow on abandoned agricultural lands increase in extent. We assess how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics. Secondary forests recover remarkably fast in species richness but slowly in species composition. Secondary forests take a median time of five decades to recover the species richness of old-growth forest (80% recovery after 20 years) based on rarefaction analysis. Full recovery of species composition takes centuries (only 34% recovery after 20 years). A dual strategy that maintains both old-growth forests and species-rich secondary forests is therefore crucial for biodiversity conservation in human-modified tropical landscapes. Copyright © 2019 The Authors, some rights reserved

Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins-2

<p><b>Copyright information:</b></p><p>Taken from "Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins"</p><p>http://www.j-biomed-discovery.com/content/2/1/5</p><p>Journal of Biomedical Discovery and Collaboration 2007;2():5-5.</p><p>Published online 3 Oct 2007</p><p>PMCID:PMC2225388.</p><p></p>ed in nine rows to show extent of repetition of repeat units. Letters below rectangle indicate consensus sequence derived by Miller, McLachlan, and Klug (1985); dashes in consensus sequence indicate positions of no consensus. Shaded letters highlight acids that match the consensus sequence; letters in small gray rectangles indicate acids that do not match the consensus sequence but match at least one other acid in that position; unshaded letters match neither the consensus sequence nor any other acid. Blanks indicate gaps in the alignment, with the gaps positioned to maximize match of surrounding acids with the consensus sequence. Asterisks do not represent acids but indicate positions at which "insertions" commonly occur. Adapted from Figure 3 of Miller, McLachlan, and Klug (1985). B: Model of the arrangement of amino acids 103 to 204 in transcription factor IIIA of oocytes. Three complete "zinc fingers" are shown. Adapted from Figure 4 of Miller, McLachlan, and Klug (1985). Note that the amino acids that most consistently match the consensus sequence in A are those that serve as ligands with zinc in B

Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins-1

<p><b>Copyright information:</b></p><p>Taken from "Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins"</p><p>http://www.j-biomed-discovery.com/content/2/1/5</p><p>Journal of Biomedical Discovery and Collaboration 2007;2():5-5.</p><p>Published online 3 Oct 2007</p><p>PMCID:PMC2225388.</p><p></p>s of the mean values for those distributions. Similarity-based characterization of these populations focuses on the distributions, whereas identity-based characterization focuses on the means and treats the distribution as noise or as aberrant values

Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins-0

<p><b>Copyright information:</b></p><p>Taken from "Generalization through similarity: motif discourse in the discovery and elaboration of zinc finger proteins"</p><p>http://www.j-biomed-discovery.com/content/2/1/5</p><p>Journal of Biomedical Discovery and Collaboration 2007;2():5-5.</p><p>Published online 3 Oct 2007</p><p>PMCID:PMC2225388.</p><p></p>ed in nine rows to show extent of repetition of repeat units. Letters below rectangle indicate consensus sequence derived by Miller, McLachlan, and Klug (1985); dashes in consensus sequence indicate positions of no consensus. Shaded letters highlight acids that match the consensus sequence; letters in small gray rectangles indicate acids that do not match the consensus sequence but match at least one other acid in that position; unshaded letters match neither the consensus sequence nor any other acid. Blanks indicate gaps in the alignment, with the gaps positioned to maximize match of surrounding acids with the consensus sequence. Asterisks do not represent acids but indicate positions at which "insertions" commonly occur. Adapted from Figure 3 of Miller, McLachlan, and Klug (1985). B: Model of the arrangement of amino acids 103 to 204 in transcription factor IIIA of oocytes. Three complete "zinc fingers" are shown. Adapted from Figure 4 of Miller, McLachlan, and Klug (1985). Note that the amino acids that most consistently match the consensus sequence in A are those that serve as ligands with zinc in B