Decoding resilience: ecology, regulation, and evolution of biosynthetic gene clusters.

Secondary metabolism is crucial for plant survival and can generate chemistry with nutritional, therapeutic, and industrial value. Biosynthetic genes of selected secondary metabolites cluster within localised chromosomal regions. The arrangement of these biosynthetic gene clusters (BGCs) challenges the long-held model of random gene order in eukaryotes, raising questions about their regulation, ecological significance, and evolution.

Role of PMR4 and PDLP1 in priming of early acting penetration defense by resistance-inducing β-amino acids.

R-β-homoserine (RBH) and β-aminobutyric acid (BABA) induce resistance against the oomycete () in Arabidopsis, which is based on priming of multiple defense layers, including early acting penetration resistance at the cell wall. Here, we have examined the molecular basis of RBH- and BABA-primed defense by cell wall papillae against . Three-dimensional reconstruction of -induced papillae by confocal microscopy revealed no structural differences between control-, RBH-, and BABA-treated plants after challenge.

Exploring Rotational Diffusion with Plasmonic Coupling.

Measuring the orientation dynamics of nanoparticles and nonfluorescent molecules in real time with optical methods is still a challenge in nanoscience and biochemistry. Here, we examine optoplasmonic sensing taking the rotational diffusion of plasmonic nanorods as an experimental model. Our detection method is based on monitoring the dark-field scattering of a relatively large sensor gold nanorod (GNR) (40 nm in diameter and 112 nm in length) as smaller plasmonic nanorods cross its near field.

Mucoromycotina 'fine root endophytes': a new molecular model for plant-fungal mutualisms?

The most studied plant-fungal symbioses to date are the interactions between plants and arbuscular mycorrhizal (AM) fungi of the Glomeromycotina clade. Advancements in phylogenetics and microbial community profiling have distinguished a group of symbiosis-forming fungi that resemble AM fungi as belonging instead to the Mucoromycotina. These enigmatic fungi are now known as Mucoromycotina 'fine root endophytes' and could provide a means to understand the origins of plant-fungal symbioses.

Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews.

Objective: To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins.

Data Sources: MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search.

Study Selection: Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected.

PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

Objective: To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care.

Methods: Following the Institute of Medicine's , a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective.

An evolutionary epigenetic clock in plants.

Molecular clocks are the basis for dating the divergence between lineages over macroevolutionary timescales (~10 to 10 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes display a clocklike behavior.

Heritable induced resistance in : Tips and tools to improve effect size and reproducibility.

Over a decade ago, three independent studies reported that pathogen- and herbivore-exposed produces primed progeny with increased resistance. Since then, heritable induced resistance (h-IR) has been reported across numerous plant-biotic interactions, revealing a regulatory function of DNA (de)methylation dynamics. However, the identity of the epi-alleles controlling h-IR and the mechanisms by which they prime defense genes remain unknown, while the evolutionary significance of the response requires confirmation.

Epigenetic processes in plant stress priming: Open questions and new approaches.

Priming reflects the capacity of plants to memorise environmental stress experience and improve their response to recurring stress. Epigenetic modifications in DNA and associated histone proteins may carry short-term and long-term memory in the same plant or mediate transgenerational effects, but the evidence is still largely circumstantial. New experimental tools now enable scientists to perform targeted manipulations that either prevent or generate a particular epigenetic modification in a particular location of the genome.

Who provides chronic disease management? Population-based retrospective cohort study in Alberta.

Objective: To determine the proportions of patients who receive care from family physicians, specialists, and nurse practitioners for the management of common chronic medical conditions.

Design: Population-based retrospective cohort study.

Setting: Province of Alberta.

An evolutionary epigenetic clock in plants.

Molecular clocks are the basis for dating the divergence between lineages over macro-evolutionary timescales (~10 -10 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes possess a clock-like behavior.

Long-lasting memory of jasmonic acid-dependent immunity requires DNA demethylation and ARGONAUTE1.

Stress can have long-lasting impacts on plants. Here we report the long-term effects of the stress hormone jasmonic acid (JA) on the defence phenotype, transcriptome and DNA methylome of Arabidopsis. Three weeks after transient JA signalling, 5-week-old plants retained induced resistance (IR) against herbivory but showed increased susceptibility to pathogens.

Predicting Antiviral Resistance Mutations in SARS-CoV-2 Main Protease with Computational and Experimental Screening.

The main protease (M) of SARS-CoV-2 is essential for viral replication and has been the focus of many drug discovery efforts since the start of the COVID-19 pandemic. Nirmatrelvir (NTV) is an inhibitor of SARS-CoV-2 M that is used in the combination drug Paxlovid for the treatment of mild to moderate COVID-19. However, with increased use of NTV across the globe, there is a possibility that future SARS-CoV-2 lineages will evolve resistance to NTV.

A single amino acid transporter controls the uptake of priming-inducing beta-amino acids and the associated tradeoff between induced resistance and plant growth.

Selected β-amino acids, such as β-aminobutyric acid (BABA) and R-β-homoserine (RBH), can prime plants for resistance against a broad spectrum of diseases. Here, we describe a genome-wide screen of fully annotated Arabidopsis thaliana T-DNA insertion lines for impaired in RBH-induced immunity (iri) mutants against the downy mildew pathogen Hyaloperonospora arabidopsidis, yielding 104 lines that were partially affected and four lines that were completely impaired in RBH-induced resistance (IR). We confirmed the iri1-1 mutant phenotype with an independent T-DNA insertion line in the same gene, encoding the high-affinity amino acid transporter LYSINE HISTIDINE TRANSPORTER 1 (LHT1).

Ancestral Sequence Reconstruction Identifies Structural Changes Underlying the Evolution of PETase and Variants with Improved Stability and Activity.

The improved production, recycling, and removal of plastic waste, such as polyethylene terephthalate (PET), are pressing environmental and economic issues for society. Biocatalytic (enzymatic) PET depolymerization is potentially a sustainable, low-energy solution to PET recycling, especially when compared with current disposal methods such as landfills, incineration, or gasification. IsPETase has been extensively studied for its use in PET depolymerization; however, its evolution from cutinases is not fully understood, and most engineering studies have neglected the majority of the available sequence space remote from the active site.

Immune priming in plants: from the onset to transgenerational maintenance.

Enhancing plant resistance against pests and diseases by priming plant immunity is an attractive concept for crop protection because it provides long-lasting broad-spectrum protection against pests and diseases. This review provides a selected overview of the latest advances in research on the molecular, biochemical and epigenetic drivers of plant immune priming. We review recent findings about the perception and signalling mechanisms controlling the onset of priming by the plant stress metabolite β-aminobutyric acid.

Long-Lasting Defence Priming by β-Aminobutyric Acid in Tomato Is Marked by Genome-Wide Changes in DNA Methylation.

Exposure of plants to stress conditions or to certain chemical elicitors can establish a primed state, whereby responses to future stress encounters are enhanced. Stress priming can be long-lasting and likely involves epigenetic regulation of stress-responsive gene expression. However, the molecular events underlying priming are not well understood.

Transcriptomic changes during the establishment of long-term methyl jasmonate-induced resistance in Norway spruce.

Norway spruce (Picea abies) is an economically and ecologically important tree species that grows across northern and central Europe. Treating Norway spruce with jasmonate has long-lasting beneficial effects on tree resistance to damaging pests, such as the European spruce bark beetle Ips typographus and its fungal associates. The (epi)genetic mechanisms involved in such long-lasting jasmonate induced resistance (IR) have gained much recent interest but remain largely unknown.

PEER simplified chronic pain guideline: Management of chronic low back, osteoarthritic, and neuropathic pain in primary care.

Objective: To develop a clinical practice guideline to support the management of chronic pain, including low back, osteoarthritic, and neuropathic pain in primary care.

Methods: The guideline was developed with an emphasis on best available evidence and shared decision-making principles. Ten health professionals (4 generalist family physicians, 1 pain management-focused family physician, 1 anesthesiologist, 1 physical therapist, 1 pharmacist, 1 nurse practitioner, and 1 psychologist), a patient representative, and a nonvoting pharmacist and guideline methodologist comprised the Guideline Committee.