Non-target-site resistance (NTSR) to herbicides in weeds can be conferred as a result of the alteration of one or more physiological processes, including herbicide absorption, translocation, sequestration, and metabolism. The mechanisms of NTSR are generally more complex to decipher than target-site resistance (TSR) and can impart cross-resistance to herbicides with different modes of action. Metabolism-based NTSR has been reported in many agriculturally important weeds, although reduced translocation and sequestration of herbicides has also been found in some weeds. This review focuses on summarizing the recent advances in our understanding of the physiological, biochemical, and molecular basis of NTSR mechanisms found in weed species. Further, the importance of examining the co-existence of TSR and NTSR for the same herbicide in the same weed species and influence of environmental conditions in the altering and selection of NTSR is also discussed. Knowledge of the prevalence of NTSR mechanisms and co-existing TSR and NTSR in weeds is crucial for designing sustainable weed management strategies to discourage the further evolution and selection of herbicide resistance in weeds.

Evolution of multiple herbicide resistance in Palmer amaranth across the United States is a serious challenge for its management. Recently, a Palmer amaranth population (KCTR; Kansas Conservation Tillage Resistant) from a long-term conservation tillage research project in Kansas, United States, was found uncontrolled by several commonly used herbicides. Importantly, this field did not have a history of repeated use of some of the herbicides for which the KCTR Palmer amaranth population showed lack of control. The objectives of this study were to confirm the evolution of multiple resistances and determine possible mechanism(s) of resistance in KCTR Palmer amaranth plants. In response to post-emergence application, 28–100% of KCTR Palmer amaranth survived field recommended rates of 2,4-D, ALS-, PS II-, EPSPS-, PPO-, HPPD-inhibitor herbicides, or tank- or pre-mixture of PS II- and HPPD-inhibitor herbicides, confirming evolution of six-way resistance in this Palmer amaranth population. However, this population was found susceptible to the PS I- and glutamine synthetase inhibitor herbicides. Chlorsulfuron-, imazethapyr-, and atrazine-resistant plants did not show any previously reported mutation in ALS and psbA genes, the target sites of these herbicides, respectively. However, the survivors of glyphosate treatment showed amplification of EPSPS gene (up to 88 copies). The KCTR plants pretreated with cytochrome P450 or GST inhibitors along with atrazine, 2,4-D, lactofen, or mesotrione had significantly less biomass accumulation than those treated with herbicides alone. Plants treated with P450 inhibitor followed by imazethapyr showed moderate reduction of biomass in KCTR which was statistically similar to a susceptible Palmer amaranth population treated with imazethapyr. These results suggest predominance of metabolic resistance possibly mediated by cytochrome P450 and GST enzyme activity that may have predisposed the KCTR Palmer amaranth population to evolve resistance to multiple herbicides. This is the first report of evolution of six-way resistance in a single Palmer amaranth population. Appropriate management strategies, including integration of cultural, and mechanical, and herbicide mixtures, are warranted to control such Palmer amaranth populations.

The present study was undertaken to retrospectively evaluate the frequency and pattern of infections in 309 patients with systemic lupus erythematosus (SLE) attending the Rheumatology Clinic of the All India Institute of Medical Sciences Hospital between January 1989 and May 1994. Eighty-two patients (26.5%) were found to be suffering from one or more infections during this period. Tuberculosis was the commonest infection observed. Seventy-four patient (23.9%) had a single infection, while 8 (2.6%) had multiple infections. The infection rate was found to be higher among patients with SLE and major organ involvement than among those with mild superficial SLE.

A Palmer amaranth (Amaranthus palmeri S. Watson) population (KCTR: KS Conservation Tillage Resistant) collected from a conservation tillage field was confirmed with resistance to herbicides from at least six sites of action, including 2,4-D. The objectives of this research were using KCTR A. palmeri to investigate i) the level of 2,4-D resistance, ii) 2,4-D absorption and translocation profiles, iii) the rate of 2,4-D metabolism compared with 2,4-D-tolerant wheat (Triticum aestivum L.), and iv) the possible role of cytochrome P450s (P450s) in meditating resistance. Dose-response experiments were conducted to assess the level of 2,4-D resistance in KCTR compared to susceptible plants, KSS (KS 2,4-D susceptible) and MSS (MS 2,4-D susceptible). KSS, MSS, and KCTR plants were treated with [14C] 2,4-D to determine absorption, translocation, and metabolic patterns. Additionally, whole-plant dose-response assays were conducted by treating KCTR and KSS plants with P450-inhibitors (malathion, piperonyl butoxide: PBO) prior to 2,4-D application. Dose-response experiments indicated a 6 to 11-fold 2,4-D resistance in KCTR compared to susceptible plants. No difference was found in percent [14C] 2,4-D absorption among the populations. However, 10% less and 3 times slower translocation of [14C] 2,4-D was found in KCTR compared to susceptible plants. Importantly, [14C] 2,4-D was metabolized faster in KCTR than susceptible plants. At 24, 48, and 72 hours after treatment (HAT), KCTR metabolized ∼20-30% more [14C] 2,4-D than susceptible plants. KCTR plants and wheat generated metabolites with similar polarity. Nonetheless, at 24 HAT, ∼70% of [14C] 2,4-D was metabolized in wheat, compared to only 30% in KCTR A. palmeri. Application of malathion prior to 2,4-D increased the sensitivity to 2,4-D in KCTR, suggesting involvement of P450s in mediating 2,4-D metabolism. However, no such impact of PBO was documented. Overall, this study confirms that enhanced metabolism is the primary mechanism of 2,4-D resistance in KCTR.

Glyphosate-resistant (GR) Palmer amaranth is a problematic annual broadleaf weed in soybean production fields in Nebraska and many other states in the United States. Soybean resistant to 2,4-D, glyphosate, and glufosinate (Enlist E3TM) has been developed and was first grown commercially in 2019. The objectives of this research were to evaluate the effect of herbicide programs applied PRE, PRE followed by (fb) late-POST (LPOST), and early-POST (EPOST) fb LPOST on GR Palmer amaranth control, density, and biomass reduction, soybean injury, and yield. Field experiments were conducted near Carleton, Nebraska in 2018, and 2019 in a grower’s field infested with GR Palmer amaranth in 2,4-D, glyphosate, and glufosinate-resistant soybean. Sulfentrazone + cloransulam-methyl, imazethapyr + saflufenacil + pyroxasulfone, and chlorimuron ethyl + flumioxazin + metribuzin applied PRE provided 84% to 97% control of GR Palmer amaranth compared to the nontreated control 14 d after PRE. Averaged across herbicide programs, PRE fb 2,4-D and/or glufosinate, and sequential application of 2,4-D or glufosinate applied EPOST fb LPOST resulted in 92% and 88% control of GR Palmer amaranth, respectively, compared with 62% control with PRE-only programs 14 d after LPOST. Reductions in Palmer amaranth biomass followed the same trend; however, Palmer amaranth density was reduced 98% in EPOST fb LPOST programs compared to 91% reduction in PRE fb LPOST and 76% reduction in PRE-only programs. PRE fb LPOST and EPOST fb LPOST programs resulted in an average soybean yield of 4,478 and 4,706 kg ha−1, respectively, compared with 3,043 kg ha−1 in PRE-only programs. Herbicide programs evaluated in this study resulted in no soybean injury. The results of this research illustrate that herbicide programs are available for the management of GR Palmer amaranth in 2,4-D, glyphosate, and glufosinate-resistant soybean.