Qin Yu

Modern herbicides make major contributions to global food production by easily removing weeds and substituting for destructive soil cultivation. However, persistent herbicide selection of huge weed numbers across vast areas can result in the rapid evolution of herbicide resistance. Herbicides target specific enzymes, and mutations are selected that confer resistance-endowing amino acid substitutions, decreasing herbicide binding. Where herbicides bind within an enzyme catalytic site very few mutations give resistance while conserving enzyme functionality. Where herbicides bind away from a catalytic site many resistance-endowing mutations may evolve. Increasingly, resistance evolves due to mechanisms limiting herbicide reaching target sites. Especially threatening are herbicide-degrading cytochrome P450 enzymes able to detoxify existing, new, and even herbicides yet to be discovered. Global weed species are accumulating resistance mechanisms, displaying multiple resistance across many herbicides and posing a great challenge to herbicide sustainability in world agriculture. Fascinating genetic issues associated with resistance evolution remain to be investigated, especially the possibility of herbicide stress unleashing epigenetic gene expression. Understanding resistance and building sustainable solutions to herbicide resistance evolution are necessary and worthy challenges.

OBJECTIVES: We examined the effectiveness of the Sources of Strength suicide prevention program in enhancing protective factors among peer leaders trained to conduct schoolwide messaging and among the full population of high school students. METHODS: Eighteen high schools--6 metropolitan and 12 rural--were randomly assigned to immediate intervention or the wait-list control. Surveys were administered at baseline and 4 months after program implementation to 453 peer leaders in all schools and to 2675 students selected as representative of the 12 rural schools. RESULTS: Training improved the peer leaders' adaptive norms regarding suicide, their connectedness to adults, and their school engagement, with the largest gains for those entering with the least adaptive norms. Trained peer leaders in larger schools were 4 times as likely as were untrained peer leaders to refer a suicidal friend to an adult. Among students, the intervention increased perceptions of adult support for suicidal youths and the acceptability of seeking help. Perception of adult support increased most in students with a history of suicidal ideation. CONCLUSIONS: Sources of Strength is the first suicide prevention program involving peer leaders to enhance protective factors associated with reducing suicide at the school population level.

Acetohydroxyacid synthase (AHAS) inhibitor herbicides currently comprise the largest site-of-action group (with 54 active ingredients across five chemical groups) and have been widely used in world agriculture since they were first introduced in 1982. Resistance evolution in weeds to AHAS inhibitors has been rapid and identified in populations of many weed species. Often, evolved resistance is associated with point mutations in the target AHAS gene; however non-target-site enhanced herbicide metabolism occurs as well. Many AHAS gene resistance mutations can occur and be rapidly enriched owing to a high initial resistance gene frequency, simple and dominant genetic inheritance and lack of major fitness cost of the resistance alleles. Major advances in the elucidation of the crystal structure of the AHAS (Arabidopsis thaliana) catalytic subunit in complex with various AHAS inhibitor herbicides have greatly improved current understanding of the detailed molecular interactions between AHAS, cofactors and herbicides. Compared with target-site resistance, non-target-site resistance to AHAS inhibitor herbicides is less studied and hence less understood. In a few well-studied cases, non-target-site resistance is due to enhanced rates of herbicide metabolism (metabolic resistance), mimicking that occurring in tolerant crop species and often involving cytochrome P450 monooxygenases. However, the specific herbicide-metabolising, resistance-endowing genes are yet to be identified in resistant weed species. The current state of mechanistic understanding of AHAS inhibitor herbicide resistance is reviewed, and outstanding research issues are outlined.

Weedy plant species that have evolved resistance to herbicides due to enhanced metabolic capacity to detoxify herbicides (metabolic resistance) are a major issue. Metabolic herbicide resistance in weedy plant species first became evident in the 1980s in Australia (in Lolium rigidum) and the United Kingdom (in Alopecurus myosuroides) and is now increasingly recognized in several crop-weed species as a looming threat to herbicide sustainability and thus world crop production. Metabolic resistance often confers resistance to herbicides of different chemical groups and sites of action and can extend to new herbicide(s). Cytochrome P450 monooxygenase, glycosyl transferase, and glutathione S-transferase are often implicated in herbicide metabolic resistance. However, precise biochemical and molecular genetic elucidation of metabolic resistance had been stalled until recently. Complex cytochrome P450 superfamilies, high genetic diversity in metabolic resistant weedy plant species (especially cross-pollinated species), and the complexity of genetic control of metabolic resistance have all been barriers to advances in understanding metabolic herbicide resistance. However, next-generation sequencing technologies and transcriptome-wide gene expression profiling are now revealing the genes endowing metabolic herbicide resistance in plants. This Update presents an historical review to current understanding of metabolic herbicide resistance evolution in weedy plant species.

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I+P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action.