Contents  Summary 1 I. Introduction 2 II. Integrating defense strategies 2 III. Constitutive defense systems: first tier of defense 4 IV. Inducible defense systems: second tier of defense 11 V. Genetics and physiology of bark defense 13 VI.  Bark beetles: diminutive but deadly 15 VII. The arms race: coevolution of conifer defense and  bark beetle strategies 15 VIII. Bark‐beetle‐vectored blue‐stain fungi: multiple  attacks against multiple defenses 17 IX. Conclusions 18  Acknowledgements 19  References 19 Summary Conifers are long‐lived organisms, and part of their success is due to their potent defense mechanisms. This review focuses on bark defenses, a front line against organisms trying to reach the nutrient‐rich phloem. A major breach of the bark can lead to tree death, as evidenced by the millions of trees killed every year by specialized bark‐invading insects. Different defense strategies have arisen in conifer lineages, but the general strategy is one of overlapping constitutive mechanical and chemical defenses overlaid with the capacity to up‐regulate additional defenses. The defense strategy incorporates a graded response from ‘repel’, through ‘defend’ and ‘kill’, to ‘compartmentalize’, depending upon the advance of the invading organism. Using a combination of toxic and polymer chemistry, anatomical structures and their placement, and inducible defenses, conifers have evolved bark defense mechanisms that work against a variety of pests. However, these can be overcome by strategies including aggregation pheromones of bark beetles and introduction of virulent phytopathogens. The defense structures and chemicals in conifer bark are reviewed and questions about their coevolution with bark beetles are discussed.

This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 (GLP-1) receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed by diet and exercise alone. Two estimands addressed two efficacy-related questions: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a trial product estimand (on trial product without rescue medication use) in all randomized patients. RESEARCH DESIGN AND METHODS This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries. Adults with type 2 diabetes insufficiently controlled with diet and exercise were randomized (1:1:1:1) to once-daily oral semaglutide 3 mg, 7 mg, 14 mg, or placebo. The primary end point was change from baseline to week 26 in HbA 1c. The confirmatory secondary end point was change from baseline to week 26 in body weight. RESULTS In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA 1c 8.0% [64 mmol/mol]), oral semaglutide reduced HbA 1c (placebo-adjusted treatment differences at week 26: treatment policy estimand, 20.6% [3 mg], 20.9% [7 mg], and 21.1% [14 mg]; trial product estimand, 20.7% [3 mg], 21.2% [7 mg], and 21.4% [14 mg]; P < 0.001 for all) and body weight (treatment policy, 20.1 kg [3 mg], 20.9 kg [7 mg], and 22.3 kg [14 mg, P < 0.001]; trial product, 20.2 kg [3 mg], 21.0 kg [7 mg, P = 0.01], and 22.6 kg [14 mg, P < 0.001]). Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide. Trial product discontinuations occurred in 2.3-7.4% with oral semaglutide and 2.2% with placebo. CONCLUSIONS In patients with type 2 diabetes, oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA 1c (all doses) and body weight loss (14 mg dose) versus placebo, with a safety profile consistent with other GLP-1 receptor agonists.

No abstract

No abstract

Wounding of Norway spruce by inoculation with sterile agar, or agar containing the pathogenic fungus Ceratocystis polonica, induced traumatic resin duct formation in the stem. Visible anatomical responses occurred in the cambium 6-9 d post-inoculation. Near the inoculation site cellular proliferation, polyphenolic accumulation, and lignification were induced as a wound reaction to seal the damaged area. Five centimetres from the inoculation site cells in the cambial zone swelled and divided to form clusters. By 18 d post-inoculation, these cells began to differentiate into resin duct epithelial cells surrounding incipient schizogenous lumens. Mature axial traumatic ducts appeared by 36 d as a row of ducts in the xylem centripetal to the cambium. The ducts formed an interconnected network continuous with radial resin ducts. Parenchyma cells surrounding the ducts accumulated polyphenols that disappeared as the cells differentiated into tracheids. These polyphenols appeared to contain fewer sugar residues compared to those accumulating in the secondary phloem, as indicated by the periodic acid-Schiff's staining. The epithelial cells did not accumulate polyphenols but contained immunologically detectable phenylalanine ammonia lyase (EC 4.3.1.5), indicating synthesis of phenolics as a possible resin component. These findings may represent a defense mechanism in Norway spruce against the pathogenic fungus Ceratocystis polonica.