Multiple Sites Of Action Research Articles

Arginine-Vasotocin Neuronal System in Steindachneridion parahybae (Siluriformes: Pimelodidae) and Its Influence on Artificially Induced Spawning in Captivity

This study summarizes new data on induced spawning of Steindachneridion parahybae, focusing on the aggressive behavior of females. This study characterizes the vasotocinergic system using immunohistochemistry, highlighting the potential influence of arginine-vasotocin (AVT) on reproductive physiology. Two experimental groups were proposed: (A) control, with one female in the aquarium, and (B) experimental, with two females in the same aquarium. Dominant (D) females presented a more aggressive behavior and did not show any injury. They apparently had a length and body mass higher than injured nondominant (ND) females. The analysis identified positive AVT immunoreactive (ir) neurons exclusively within the preoptic area, including parvocellular, magnocellular, and gigantocellular subpopulations, containing fibers-ir extending into the pituitary gland. Cellular and nuclear areas were greater in D compared to ND in the magnocellular subpopulation. There were no differences between parvocellular and gigantocellular subpopulations. There was a difference on the steroid plasma profile of cortisol (more in ND than in D) and 17α,20β-dihydroxy-4-pregnen-3-one (more in D than in ND). Furthermore, control and D females presented higher optical densities for AVT-ir, gonadotropin-releasing hormone-ir, and luteinizing hormone-ir than ND. In general, there were no differences in the results of female (control group) with D females. The AVT system is highly complex, possibly counting multiple sites of action during artificial reproduction and acting directly and/or indirectly associated with behavioral and physiological changes in S. parahybae females when induced to spawning.

Synergistic Interaction of Certain Essential Oils and Their Active Compounds with Fluconazole against Azole-resistant Strains of Cryptococcus neoformans.

This study investigated the anti-cryptococcal potential of certain essential oils (EOs)/compounds alone and in combination with fluconazole. We investigated the antifungal activity of oils of Cinnamomum verum, Cymbopogon citratus, Cymbopogon martini, and Syzygium aromaticum, and their major active ingredients cinnamaldehyde, citral, eugenol, and geraniol against clinical and standard strains of Cryptococcus neoformans (CN). Disc diffusion, broth microdilution, checkerboard methods, and transmission electron microscopy were employed to determine growth inhibition, synergistic interaction, and mechanism of action of test compounds. EOs/compounds showed pronounced antifungal efficacy against azole-resistant CN in the order of cinnamaldehyde > eugenol > S. aromaticum > C. verum > citral > C. citratus > geraniol ≥ C. martini, each exhibiting zone of inhibition >15 mm. These oils/compounds were highly cidal compared to fluconazole. Eugenol and cinnamaldehyde showed the strongest synergy with fluconazole against CN by lowering their MICs up to 32-fold. Transmission electron microscopy indicated damage of the fungal cell wall, cell membrane, and other endomembranous organelles. Test oils and their active compounds exhibited potential anti-cryptococcus activity against the azole-resistant strains of CN. Moreover, eugenol and cinnamaldehyde significantly potentiated the anti-cryptococcal activity of fluconazole. It is suggested that multiple sites of action from oils/compounds could turn static fluconazole into a cidal drug combination in combating cryptococcosis.

Preparation of a bis-triazolyl bridged β-cyclodextrin stationary phase and its application for enantioseparation of chiral compounds by HPLC.

A novel bis-triazolyl bridged β-cyclodextrin was first synthesized by the Click reaction between azido-β-cyclodextrin and 1,6-heptadiyne. Then it was bonded onto silica gel to obtain a bis-triazolyl bridged β-cyclodextrin-based chiral stationary phase (BCDP). After structure characterization, the HPLC performance of BCDP was systematically evaluated by using different types of compounds as probes. The results showed that BCDP could well separate 18 kinds of achiral aromatic compounds (homologues, positional isomers, etc.) and 35 kinds of chiral drugs or pesticides, such as triazoles (Rs = 1.33-3.15), flavanones (Rs = 1.49-2.62), dansyl amino acids (Rs = 0.96-1.99), and β-blocker drugs (Rs = 0.68-2.78). BCDP could separate a wider range of compounds (53 kinds); especially, some chiral substance pairs that were difficult to be resolved on the ordinary cyclodextrin CSPs, including triazoles containing two chiral carbons (triadimenol, bitertanol, metconazole, and triticonazole), strongly ionized amino acids (acidic Asp, alkalic Arg, and polar Thr) and β-blockers with bulky groups (carvedilol, propranolol, and pindolol). Obviously, the unique synergistic inclusion effect of bridged cyclodextrin with double cavities and the bis-triazole bridging group could provide multiple action sites, such as hydrogen bonding, π-π stacking and acid-base action sites, thus improving its chiral chromatographic performance.

Self-assembled carrier-free formulations based on medicinal and food active ingredients.

The popularity of medicinal plants, which have a unique system and are mostly used in compound form for the prevention and treatment of a wide range of diseases, is growing worldwide. In recent years, with advances in chemical separation and structural analysis techniques, many of the major bioactive molecules of medicinal plants have been identified. However, the active ingredients in medicinal plants often possess chemical characteristics, including poor water solubility, stability and bioavailability, which limit their therapeutic applications. To address this problem, self-assembly of small molecules from medicinal food sources provides a new strategy. Driven by various types of acting forces, medicinal small molecules with modifiable groups, multiple sites of action, hydrophobic side chains, and rigid backbones with self-assembly properties are able to form various supramolecular network hydrogels, nanoparticles, micelles, and other self-assemblies. This review first summarizes the forms of self-assemblies such as supramolecular network hydrogels, nanoparticles, and micelles at the level of the action site, and discusses the recent studies on the active ingredients in medicinal plants that can be used for self-assembly, in addition to summarizing the advantages of self-assemblies for a variety of disease applications, including wound healing, antitumor, anticancer, and diabetes mellitus. Finally, the problems of self-assemblers and the possible directions for future development are presented. We firmly believe that self-assemblers have the potential to develop effective compounds from drug-food homologous plants, providing valuable information for drug research and new strategies and perspectives for the modernization of Chinese medicine.

Evaluating cover crop tolerance to corn residual herbicides using field-treated soil in greenhouse bioassay

AbstractMore growers across the U.S. Midwest are considering interseeding or overseeding cover crops into corn for soil health purposes. One challenge of this practice is the potential injury from soil residual herbicides applied preemergence (PRE) for weed control in corn to the interseeded and overseeded cover crop species. Field-treated soil was collected in 2021 and 2022 at Janesville, WI, and Lancaster, WI, to investigate the impact of PRE residual herbicides on establishment of interseeded and overseeded cover crops via greenhouse bioassay. Soil samples (0 to 5 cm depth) were collected from field experiments at 0, 10, 20, 30, 40, 50, 60, and 70 days after treatment (DAT). Treatments consisted of 14 single and multiple sites of action (SOAs) PRE herbicides plus a nontreated check (NTC). Four bioindicator cover crop species were used in the greenhouse bioassay: annual ryegrass, cereal rye, radish, and red clover. Cover crop biomass was collected 28 d after bioassay seeding. Cover crop species responded differently across herbicide treatments. Annual ryegrass and cereal rye were sensitive to treatments containing herbicide Group 15, whereas Groups 2, 4, 5, 14, and 27 had minimal impact on their establishment when field soil was collected at 30 DAT (interseeding scenario) and 70 DAT (overseeding scenario) compared to the NTC. Radish and red clover were sensitive to herbicide Groups 2, 4, and 27, whereas Groups 5, 14, and 15 had minimal impact on their establishment. Annual ryegrass, radish, and red clover were more sensitive to PRE herbicides containing two and three SOAs than to herbicides with a single SOA. On the basis of these greenhouse bioassay results, cover crop species should be carefully selected depending on the soil residual herbicide when interseeded and overseeded into corn. Field studies will be conducted to validate these results and support recommendations to growers interested in this system.

Survey of target site resistance alleles conferring resistance in Poa annua

AbstractPoa annua L. (annual bluegrass) is a common weed in turfgrass and has been reported resistant to 12 different herbicide sites of action, with various combinations of multiple‐herbicide resistance having been identified. To quantify the extent of herbicide‐resistant P. annua, the ResistPoa Project (resistpoa.org) surveyed 1349 P. annua populations for resistance to nine sites of action and one plant growth retardant. Herein, we report results from sequencing of known target site mutations found in 5‐enolpyruvylshikimate‐3 phosphate synthase (EPSPS), acetolactate synthase (ALS), photosystem II protein D (psbA), and 𝛼‐tubulin genes. Populations were sequenced using either capillary or amplicon sequencing (AmpSeq), depending on the complexity of the gene, and were analyzed for target‐site resistance. After additional resistance screening, a total of 389 suspected resistant populations were sequenced—131 for ALS, 83 for EPSPS, 93 for psbA, and 82 for 𝛼‐tubulin. From the resistant populations, 64 displayed resistance to multiple sites of action. After sequencing, it was determined that target‐site resistance was the common form of resistance for all sites of action outside of psbA with 65.6% of ALS populations, 73.5% of EPSPS, 39.8% of psbA, and 91.5% of 𝛼‐tubulin having presented a target‐site mutation.

Peripheral clock disruption and metabolic disease: moving beyond the anatomy to a functional approach.

Sleep and circadian disruption are associated with an increased risk of metabolic disease, including obesity and diabetes. Mounting evidence indicates that misaligned and/or non-functional clock proteins in peripheral tissues critically contribute to the presentation of metabolic disease. Many of the foundational studies which led to this conclusion have focused on specific tissues such as the adipose, pancreas, muscle, and liver. While these studies have greatly advanced the field, the use of anatomical markers to manipulate tissue-specific molecular clocks may not be representative of the circadian disruption that occurs within the clinical population. In this manuscript, we argue that investigators can gain a better understanding of the consequences of sleep and circadian disruption by targeting groups of cells with a functional relationship, even if those cells go beyond anatomical boundaries. This approach is especially important when considering metabolic outcomes which rely on endocrine signaling molecules, such as leptin, that have multiple sites of action. Through the review of several studies, as well as our own work, this article reframes peripheral clock disruption from a functional approach. We additionally present new evidence that disruption of the molecular clock within all cells expressing the leptin receptor affects leptin sensitivity in a time-dependent manner. Taken together, this perspective aims to provide new insight into the mechanisms leading to metabolic disease associated with circadian disruption and various sleep disorders.

Growth and development of multiple waterhemp (Amaranthus tuberculatus) cohorts in corn and soybeans

Waterhemp is a troublesome weed species in cropping systems throughout Wisconsin and much of the US Midwest. Coupled with extended emergence window, rapid growth, high genetic diversity, and herbicide resistance to multiple sites of action, waterhemp represents a major challenge for chemical-based weed control. The objective of this experiment was to evaluate the impact of soybean and corn canopy on growth and development of multiple waterhemp cohorts in 2019 and 2020. Treatments consisted of narrow- (38 cm row spacing) and wide-row (76 cm row spacing) soybeans, corn (76 cm row spacing), and fallow (no crop), with 6 waterhemp transplant timings (cohorts) in 2019 and 2020, respectively. Waterhemp seedlings grown in the greenhouse were transplanted at the 2-3 true leaves growth stage to the field at 10-day increments throughout the typical waterhemp emergence season for Wisconsin (June-July). Waterhemp plants were measured for height and harvested for biomass when they reached the flowering stage. The number of days from the first transplant timing to result in 50% and 90% biomass and height reduction (ED50 and ED90) of subsequent waterhemp cohorts were estimated and used as indicators of weed suppression ability by the respective crop. Narrow-row soybeans required fewer days to suppress 50% growth of new waterhemp cohorts followed by corn, wide row soybeans, and fallow, respectively (4, 6, 9, and 14 d for 50% biomass reduction, and 10, 14, 18, and 42 d for 50% height reduction, respectively). Similarly, narrow-row soybeans required fewer days to suppress 90% biomass of waterhemp, followed by corn, wide-row soybeans, and fallow (11, 15, 18, and 78 d, respectively). Conversely, narrow and wide-row soybeans required fewer days to suppress 90% height of new waterhemp cohorts followed by corn and fallow (20, 26, 43, and 85 d, respectively). Rapid soybean canopy closure (e.g., planting soybeans earlier and in narrow row-spacing) combined with other integrated weed management practices have the potential to reduce reliance on POST herbicide application and mitigate herbicide resistance evolution. In corn, mid- to late-season monitoring and management of later emerging waterhemp cohorts is recommended due to longer time required to reach 90% waterhemp growth suppression.

Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system.

Omega-3 polyunsaturated fatty acids (PUFAs) can play important roles in maintaining mental health and resistance to stress, and omega-3 PUFAs supplementation can display beneficial effects on both the prevention and treatment of depressive disorders. Although the underlying mechanisms are still unclear, accumulated evidence indicates that omega-3 PUFAs can exhibit pleiotropic effects on the neural structure and function. Thus, they play fundamental roles in brain activities involved in the mood regulation. Since depressive symptoms have been assumed to be of central origin, this review aims to summarize the recently published studies to identify the potential neurobiological mechanisms underlying the anti-depressant effects of omega-3 PUFAs. These include that of (1) anti-neuroinflammatory; (2) hypothalamus-pituitary-adrenal (HPA) axis; (3) anti-oxidative stress; (4) anti-neurodegeneration; (5) neuroplasticity and synaptic plasticity; and (6) modulation of neurotransmitter systems. Despite many lines of evidence have hinted that these mechanisms may co-exist and work in concert to produce anti-depressive effects, the potentially multiple sites of action of omega-3 PUFAs need to be fully established. We also discussed the limitations of current studies and suggest future directions for preclinical and translational research in this field.

Multi-target action of β-alanine protects cerebellar tissue from ischemic damage

Brain ischemic stroke is among the leading causes of death and long-term disability. New treatments that alleviate brain cell damage until blood supply is restored are urgently required. The emerging focus of anti-stroke strategies has been on blood-brain-barrier permeable drugs that exhibit multiple sites of action. Here, we combine single-cell electrophysiology with live-cell imaging to find that β-Alanine (β-Ala) protects key physiological functions of brain cells that are exposed to acute stroke-mimicking conditions in ex vivo brain preparations. β-Ala exerts its neuroprotective action through several distinct pharmacological mechanisms, none of which alone could reproduce the neuroprotective effect. Since β-Ala crosses the blood-brain barrier and is part of a normal human diet, we suggest that it has a strong potential for acute stroke treatment and facilitation of recovery.

Multifunctional β-Cyclodextrin Polymer for Simultaneous and Effective Removal of Organic Micropollutants, Heavy Metals, and Detrimental Microorganisms from Water

A new porous β-cyclodextrin-based polymer (PCD-Gs) adsorbent was synthesized by the copolymerization of allyl-β-CD and partially allylated gallic acid under different monomer feeding ratios. With a series of single-factor experiments, it was found that the PCD-Gs not only exhibited ultrarapid and efficient absorption capacity for bisphenol A and Cd(II) but also possessed strong bactericidal ability and good resistance to salt and acid. Multivariate analyses showed that there was no competitive adsorption but a positive effect between Cd(II) and bisphenol A on PCD-Gs in the binary system. Besides, the PCD-Gs had outstanding regeneration ability and removal efficiency even at environmentally relevant concentrations. Combined with 1H NMR analysis, a multimechanism was suggested that the polymer of PCD-Gs possesses multiple action sites and presents great potential for simultaneously and effectively removing organic micropollutants, metal ions, and detrimental microorganisms from contaminated water, which contributes to deep purification of water and simplification of the water treatment process.

Identification of field resistance to HPPD-inhibiting herbicides in wild radish (Raphanus raphanistrum)

AbstractThe control of multiple-resistant wild radish (Raphanus raphanistrum L.) populations in no-till Australian wheat (Triticum aestivum L.) crops has relied upon 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides over the last decade. Two R. raphanistrum populations identified as putatively resistant to pyrasulfotole + bromoxynil in an initial large-scale screening trial were characterized and confirmed to be 5- to 8-fold (comparison of LD50 values) less sensitive than the susceptible control population to the HPPD inhibitor pyrasulfotole when plants were treated at the 4-leaf stage. The two pyrasulfotole-resistant populations exhibited up to 4-fold resistance to the coformulated herbicide mixture pyrasulfotole + bromoxynil and up to 9- and 11-fold cross-resistance to mesotrione and topramezone postemergence, respectively. A small-plot trial was conducted in the field from which of one of the populations suspected of resistance was originally collected. Pyrasulfotole + bromoxynil or topramezone + bromoxynil applied postemergence delivered reduced R. raphanistrum control (79% to 87%), whereas mesotrione applied preemergence was >99% effective. We report here the first case of field resistance to HPPD-inhibiting herbicides in R. raphanistrum, caused by 12 yr of continuous reliance on that mode of action. The mitigation of herbicide resistance in continuous no-till cropping requires a constant optimization of the herbicide technology via alternation and mixtures of multiple sites of action, use of preemergence herbicides, and ensuring postemergence herbicides are applied at the most sensitive plant growth stages.

Ketamine and Its Emergence in the Field of Neurology.

The quest for a safe and effective anesthetic medication in the mid-20th century led to the discovery of CI-581, which was later named ketamine. Ketamine was labeled a “dissociative anesthetic” due to the state of sensory deprivation that it induces in the subjects receiving it. Although it enjoyed widespread use at the beginning of the Vietnam war, its use rapidly waned due to its psychedelic effect and it became more popular as a recreational drug, and in the field of veterinary medicine. However, as we gained more knowledge about its multiple sites of action, it has reemerged as a useful anesthetic/analgesic agent. In the last decade, the field of neurology has witnessed the growing use of ketamine for the treatment of several neurological conditions including migraine, status epilepticus, stroke, and traumatic brain injury (TBI). Ketamine acts primarily as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. The binding of ketamine to NMDA receptors leads to decreased frequency and duration of Ca+2 channel opening and thus inhibits glutaminergic transmission. This mechanism has proven to be neuroprotective in several neurological conditions. Ketamine does not increase intracranial pressure (ICP), and it maintains cerebral perfusion pressure (CPP) by increasing cerebral blood flow. Ketamine has also been shown to inhibit massive slow waves of neurological depolarizations called cortical spreading depolarizations (CSD), usually seen during acute neurological injury and are responsible for further neurological deterioration. Unlike other anesthetic agents, ketamine does not cause cardiac or respiratory suppression. All these favorable mechanisms and cerebral/hemodynamic actions have led to increased interest among clinicians and researchers regarding the novel uses of ketamine. This review will focus on the use of ketamine for various neurological indications.

Economics of reducing Palmer amaranth seed production in dicamba/glufosinate/glyphosate‐resistant soybean

AbstractIncreased prevalence of glyphosate‐resistant (GR) weeds within agronomic cropping systems has led to the readoption of pre‐emergence (PRE) herbicides and use of multiple herbicide‐resistant soybean [Glycine max (L.) Merr.] cultivars. Herbicide programs were evaluated in the recently commercialized dicamba/glyphosate/glufosinate‐resistant (DGGR) soybean for weed control, reduction of Palmer amaranth (Amaranthus palmeri S. Watson) seed production, crop safety, and economic performance. At 35 days after pre‐emergence herbicides, acetochlor plus dicamba plus metribuzin, acetochlor/fomesafen plus dicamba, dicamba plus flumioxazin, and imazethapyr/pyroxasulfone/saflufenacil provided 80–99% control of velvetleaf (Abutilon theophrasti Medik.), Palmer amaranth, common lambsquarters (Chenopodium album L.), and Poaceae species. Evaluation at 14 days after early postemergence herbicides indicated PRE followed by (fb) POST applications of mixtures of acetochlor, dicamba, glufosinate, and glyphosate provided 80–99% weed control compared with 67–93% control in POST‐only programs. Most herbicide programs provided 83–99% control of grass and broadleaf weeds, with 85–91% weed biomass reductions at 28 days after late‐POST. The PRE fb POST programs reduced Palmer amaranth seed production by 94–99%, whereas POST‐only programs provided 75–83% reduction. In 2020, most programs provided gross profit margins ≥US$1,000 ha−1, with glufosinate fb glufosinate and imazethapyr/pyroxasulfone/saflufenacil fb acetochlor plus glufosinate providing $1,481 and $1,466 ha−1, respectively. Benefit/cost ratios ranged between 0.3 and 3.9 in 2019 due to hail but increased to 2.9–10.9 in 2020. Results of this study support use of PRE herbicides with multiple sites of action in DGGR soybean and indicate that glufosinate can provide POST control of GR Palmer amaranth.

Confirmation of glufosinate-resistant Palmer amaranth and response to other herbicides

AbstractThe ability of weed populations to evolve resistance to herbicides affects management strategies and the profitability of crop production. The objective of this research was to screen Palmer amaranth accessions from Arkansas for glufosinate resistance. Additional efforts focused on the effectiveness of various herbicides, across multiple sites of action (SOAs), on each putative-resistant accession. The three putative accessions were selected from 60 Palmer amaranth accessions collected in 2019 and 2020 and screened with to 0.5× and 1× rates of glufosinate. A dose-response experiment was conducted for glufosinate on accessions A2019, A2020, and B2020. The effectiveness of various preemergence- and postemergence-applied herbicides were evaluated on each accession. Resistance ratios of A2019, A2020, and B2020 to glufosinate ranged from 5.1 to 27.4 when comparing LD50 values to two susceptible accessions, thus all three accessions were resistant to glufosinate. All three accessions (A2019, A2020, and B2020) were found to have a reduction equal to or greater than 20 percentage points in mortality to at least one herbicide from five different SOAs equal to or greater than five sites of action. Herbicides from nine different SOAs controlled A2019 at least 20 percentage points less than the susceptible accessions, which points to a need for additional research to characterize the response of this accession.

Response of smooth pigweed (Amaranthus hybridus) accessions from Argentina to herbicides from multiple sites of action

AbstractSmooth pigweed is one of the most troublesome weeds in Argentina. The objective of this study was to evaluate the sensitivity of 50 smooth pigweed accessions to fomesafen, topramezone, glyphosate, 2,4-D, and dicamba. Accessions were collected from soybean fields in various cropping areas in Argentina. The herbicide treatments included 2,4-D (1,140 g ae ha−1), dicamba (560 g ae ha−1), fomesafen (250 g ai ha−1), topramezone (34 g ai ha−1), and glyphosate (1,080 g ae ha−1). Plant survival was evaluated 30 d after each treatment application. Of the smooth pigweed accessions tested, 84% and 76% were susceptible (0% survival) to 2,4-D and dicamba, respectively. More than 90% of the accessions showed high (>60%) survival to glyphosate. While none of the accessions showed total sensitivity (0% survival) to the other herbicides evaluated, 43% and 72% of the accessions showed greater than 60% survival to fomesafen and topramezone, respectively. The differences in survival among accessions confirm the existence of genetic variability in Argentinian smooth pigweed and suggest that weed management practices should be prioritized to preserve the efficacy of these commonly used herbicides.

Thiobencarb resistance mechanism is distinct from CYP81A-based cross-resistance in late watergrass (Echinochloa phyllopogon)

AbstractThe genetic and molecular basis of resistance evolution in weeds to multiple herbicides remains unclear despite being a great threat to agriculture. A population of late watergrass [Echinochloa phyllopogon(Stapf.) Koso-Pol.] was reported to exhibit resistance to ≥15 herbicides from six sites of action, including thiobencarb (TB). While previous studies disclosed that the resistance to a majority of herbicides such as acetolactate synthase (ALS) and acetyl-CoA carboxylase inhibitors is caused by the overexpression of herbicide-metabolizing cytochrome P450s (CYP81A12andCYP81A21), the resistance mechanisms to some herbicides remain unknown. Here, we analyzed the resistance segregation in the progenies between resistant and sensitive populations and performed a transgenic plant sensitivity assay to resolve whether TB resistance is endowed by the sameCYP81A12/21-based cross-resistance mechanism or other unknown multiple-resistance mechanisms. In the F6progenies, resistance to the ALS inhibitor bensulfuron-methyl cosegregated with the resistances to many other herbicides under theCYP81A12/21-based cross-resistance mechanism; however, TB resistance segregated independently. Furthermore,CYP81A12/21failed to confer TB resistance in transgenicArabidopsis thalianaL. Heynh, thus confirming that TB resistance in resistantE. phyllopogonis not endowed by the two P450s that are responsible for the metabolism-based cross-resistance. This study provides evidence that resistance inE. phyllopogonto herbicides with multiple sites of action is endowed by both P450-based and other uncharacterized non–target site based mechanisms. Our findings add another layer in the understanding of resistance evolution to multiple herbicides inE. phyllopogon. Identification of the key genes endowing TB resistance will be the future direction of this research.

The Frequency-Dependence of Pre- and Postganglionic Nerve Stimulation of Pig and Rat Bladder.

PurposeThe urinary bladder generates phasic contractions via action potentials generated in pre- and then postganglionic neurons. Whilst the frequency-dependence of postganglionic neurons to generate contractions has been quantified, the dynamic range of preganglionic neurons is less clear and if intramural ganglia exert frequency-dependent modulation of transmission between pre- and postganglionic neurons. The phosphodiesterase type 5 inhibitor sildenafil reduces neurotransmitter release from postganglionic fibres to detrusor smooth muscle and an additional question was if there was also a preganglionic action. This study aimed to compare the frequency range of bladder contractile activation by pre- and postganglionic stimulation in pig and rat bladders and if sildenafil exerted additional preganglionic actions.MethodsAn arterially-perfused ex vivo pig bladder preparation was used for preganglionic (pelvic nerve) and mixed pre-and postganglionic (direct bladder wall) stimulation at 36°C and postganglionic mediated contractions achieved by field-stimulation of in vitro isolated detrusor strips. With rats, pelvic nerve stimulation was carried out in vivo and postganglionic stimulation also with isolated detrusor strips.ResultsAll contractions were abolished by 2% lignocaine indicating they are nerve-mediated. Stimulation targets were verified with hexamethonium that completely abolished pelvic nerve responses by had no effect on detrusor strips; responses to mixed bladder wall stimulation were partially reduced. The frequency-dependence of contractile activation was similar whether by pre- or postganglionic stimulation in both pigs and rats. Sildenafil reduced contractions to preganglionic stimulation significantly more than to postganglionic stimulation. Mixed pre- and postganglionic stimulation were reduced by an intermediate extent.ConclusionsIntramural ganglia offer no frequency-dependent modulation under the experimental conditions used here and the sildenafil data are consistent with multiple sites of action underlying generation of bladder contractions. A translational aspect of these findings is discussed in terms of setting stimulation parameters for neuromodulation protocols.

Mining RNA-Seq Data to Depict How Penicillium digitatum Shapes Its Transcriptome in Response to Nanoemulsion.

Penicillium digitatum is the most severe pathogen that infects citrus fruits during storage. It can cause fruit rot and bring significant economic losses. The continuous use of fungicides has resulted in the emergence of drug-resistant strains. Consequently, there is a need to develop naturally and efficiently antifungal fungicides. Natural antimicrobial agents such as clove oil, cinnamon oil, and thyme oil can be extracted from different plant parts. They exhibited broad-spectrum antimicrobial properties and have great potential in the food industry. Here, we exploit a novel cinnamaldehyde (CA), eugenol (EUG), or carvacrol (CAR) combination antifungal therapy and formulate it into nanoemulsion form to overcome lower solubility and instability of essential oil. In this study, the antifungal activity evaluation and transcriptional profile of Penicillium digitatum exposed to compound nanoemulsion were evaluated. Results showed that compound nanoemulsion had a striking inhibitory effect on P. digitatum in a dose-dependent manner. According to RNA-seq analysis, there were 2,169 differentially expressed genes (DEGs) between control and nanoemulsion-treated samples, including 1,028 downregulated and 1,141 upregulated genes. Gene Ontology (GO) analysis indicated that the DEGs were mainly involved in intracellular organelle parts of cell component: cellular respiration, proton transmembrane transport of biological process, and guanyl nucleotide-binding molecular function. KEGG analysis revealed that metabolic pathway, biosynthesis of secondary metabolites, and glyoxylate and dicarboxylate metabolism were the most highly enriched pathways for these DEGs. Taken together, we can conclude the promising antifungal activity of nanoemulsion with multiple action sites against P. digitatum. These outcomes would deepen our knowledge of the inhibitory mechanism from molecular aspects and exploit naturally, efficiently, and harmlessly antifungal agents in the citrus postharvest industry.

Control of glyphosate‐ and mesotrione‐resistant Palmer amaranth in glyphosate‐ and glufosinate‐resistant corn

AbstractIncreasing reports of herbicide‐resistant Palmer amaranth (Amaranthus palmeri S. Watson) pose a serious management concern for Kansas corn (Zea mays L.) producers. The objectives of this study were to evaluate various herbicide programs, including preemergence (PRE) alone, PRE followed by (fb) early postemergence (EPOST), and PRE fb late POST (LPOST) for control of glyphosate‐ and mesotrione‐resistant (GMR) Palmer amaranth in glyphosate‐ and glufosinate‐resistant corn, and their effect on crop injury, yield, and net economic return. Field experiments were conducted in 2018 and 2019 in grower fields with natural infestations of GMR Palmer amaranth near Seward in Stafford County, KS. Preemergence programs, including dicamba + thiencarbazone‐methyl + atrazine and dicamba + [atrazine, bicyclopyrone, mesotrione, S‐metolachlor (ABMS)] or dicamba + ABMS in mixtures with atrazine, mesotrione, S‐metolachlor, and metribuzin provided 89–93% control of GMR Palmer amaranth 3 wk after PRE. Preemergence fb EPOST programs provided 87–96% control of GMR Palmer amaranth at 2 wk after EPOST through 7 wk after LPOST. In comparison, PRE‐only programs provided 62–82% and PRE fb LPOST programs provided 75–86% control. The various herbicide programs resulted in greater corn grain yield ranging from 9,207 to 10,508 kg ha–1 compared with 6,056 kg ha–1 in the nontreated control. The highest net return ($1,300 ha–1) was achieved from dicamba + ABMS + atrazine applied PRE fb EPOST application of ABMS + atrazine. These results suggest that effective PRE fb EPOST herbicide programs consisting of multiple sites of actions are available and provide effective control of GMR Palmer amaranth in glyphosate‐ and glufosinate‐resistant corn.