RESUMEN

This paper describes the design of an innovative linear accelerator image-guided radiosurgery (IGRS) device, which is based on a composite twofold rotary gantry structure. The paper discusses five aspects of the innovative device: its overall composition, the safety net space created by the accelerator radiation head as it rotates around the patient's longitudinal axis, the non-coplanar spherical coverage in the direction of the incidence angle for quasi-4π delivery, the structural features of the composite twofold rotary gantry, and the processes of treatment planning and implementation. It elaborates on the device's manufacturing feasibility, safety, effectiveness, accuracy, and efficiency. The conclusion is that this innovative device design holds significant development value and market promotion potential.

Asunto(s)

Radiocirugia , Radiocirugia/instrumentación , Aceleradores de Partículas , Humanos , Diseño de Equipo

RESUMEN

In keeping with our investigation, a simple and practical synthesis of novel heterocyclic compounds with a sulfamoyl moiety that can be employed as insecticidal agents was reported. The compound 2-hydrazinyl-N-(4-sulfamoylphenyl)-2-thioxoacetamide 1 was coupled smoothly with triethylorthoformate or a variety of halo compounds, namely phenacyl chloride, chloroacetyl chloride, chloroacetaldehyde, chloroacetone, 1,3-dichloropropane, 1,2-dichloroethane, ethyl chloroformate, 2,3-dichloro-1,4-naphthoquinone, and chloroanil respectively, which afforded the 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives. The new products structure was determined using elemental and spectral analysis. Under laboratory conditions, the biological and toxicological effects of the synthetic compounds were also evaluated as insecticides against Spodoptera littoralis (Boisd.). Compounds 3 and 5 had LC50 values of 6.42 and 6.90 mg/L, respectively. The investigated compounds (from 2 to 11) had been undergoing molecular docking investigation for prediction of the optimal arrangement and strength of binding between the ligand (herein, the investigated compounds (from 2 to 11)) and a receptor (herein, the 2CH5) molecule. The binding affinity within docking score (S, kcal/mol) ranged between -8.23 (for compound 5), -8.12 (for compound 3) and -8.03 (for compound 9) to -6.01 (for compound 8). These compounds were shown to have a variety of binding interactions within the 2CH5 active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have 2CH5-inhibitory capabilities and hence may be used for 2CH5-targeting development. Furthermore, the three top-ranked compounds (5, 3, and 9) and the standard buprofezin were subjected to density functional theory (DFT) analysis. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy difference (ΔE) of compounds 5, 3, and 9 was found to be comparable to that of buprofezin. These findings highlighted the potential and relevance of charge transfer at the molecular level.

Asunto(s)

Diseño de Fármacos , Insecticidas , Simulación del Acoplamiento Molecular , Spodoptera , Tiadiazinas , Tiadiazoles , Animales , Insecticidas/química , Insecticidas/síntesis química , Insecticidas/farmacología , Spodoptera/efectos de los fármacos , Tiadiazoles/química , Tiadiazoles/farmacología , Tiadiazoles/síntesis química , Tiadiazinas/química , Tiadiazinas/farmacología , Tiadiazinas/síntesis química , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Proteínas de Insectos/química , Bencenosulfonamidas , Estructura Molecular , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/metabolismo , Anhidrasa Carbónica II/química

RESUMEN

Insect growth regulators (IGRs) are important green insecticides that disrupt normal growth and development in insects to reduce the harm caused by pests to crops. The ecdysone receptor (EcR) and three chitinases OfChtI, OfChtII, and OfChi-h are closely associated with the molting stage of insects. Thus, they are considered promising targets for the development of novel insecticides such as IGRs. Our previous work identified a dual-target compound 6j, which could act simultaneously on both EcR and OfChtI. In the present study, 6j was first found to have inhibitory activities against OfChtII and OfChi-h, too. Subsequently, taking 6j as a lead compound, 19 novel acetamido derivatives were rationally designed and synthesized by introducing an acetamido moiety into the amide bridge based on the flexibility of the binding cavities of 6j with EcR and three chitinases. Then, their insecticidal activities against Plutella xylostella (P. xylostella), Ostrinia furnacalis (O. furnacalis), and Spodoptera frugiperda (S. frugiperda) were carried out. The bioassay results revealed that most of these acetamido derivatives possessed moderate to good larvicidal activities against three lepidopteran pests. Especially, compound I-17 displayed excellent insecticidal activities against P. xylostella (LC50, 93.32 mg/L), O. furnacalis (LC50, 114.79 mg/L), and S. frugiperda (86.1% mortality at 500 mg/L), significantly better than that of 6j. In addition, further protein validation and molecular docking demonstrated that I-17 could act simultaneously on EcR (17.7% binding activity at 8 mg/L), OfChtI (69.2% inhibitory rate at 50 µM), OfChtII (71.5% inhibitory rate at 50 µM), and OfChi-h (73.9% inhibitory rate at 50 µM), indicating that I-17 is a potential lead candidate for novel multitarget IGRs. This work provides a promising starting point for the development of novel types of IGRs as pest management agents.

Asunto(s)

Quitinasas , Diseño de Fármacos , Proteínas de Insectos , Insecticidas , Hormonas Juveniles , Mariposas Nocturnas , Pirazoles , Spodoptera , Animales , Insecticidas/química , Insecticidas/farmacología , Insecticidas/síntesis química , Spodoptera/efectos de los fármacos , Spodoptera/crecimiento & desarrollo , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Mariposas Nocturnas/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química , Proteínas de Insectos/genética , Relación Estructura-Actividad , Hormonas Juveniles/farmacología , Hormonas Juveniles/química , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Quitinasas/metabolismo , Quitinasas/química , Quitinasas/antagonistas & inhibidores , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/química , Simulación del Acoplamiento Molecular , Larva/crecimiento & desarrollo , Larva/efectos de los fármacos , Acetamidas/farmacología , Acetamidas/química , Estructura Molecular

RESUMEN

Quantifying compatibility among control agents is essential for development of integrated pest management (IPM). Chrysoperla carnea (Siemens) and insect growth regulator insecticides are widely used in IPM of Lepidoptera. C. carnea is a generalist predator naturally present in the Mediterranean agroecosystems and bred in insectariums for commercial purposes. Here, we evaluated lethal and sublethal effects of tebufenozide on C. carnea under laboratory conditions. The treatment of eggs with tebufenozide 24 or 48 h after they were laid did not affect the hatching rate or survival of the neonate larvae. Toxic effects of tebufenozide on topically treated larvae was low; development times of surviving larvae and pupae decreased significantly compared with controls. In choice bioassays, a high percentage of third-instar larvae chose prey (Spodoptera littoralis) treated with tebufenozide in preference to untreated prey. Moreover, second-instar larvae of C. carnea that had previously consumed tebufenozide-treated prey (0.75 mL/L) had significantly reduced larval development time compared with controls, while longevity of surviving adults, fecundity and egg viability were unaffected. Ingestion of tebufenozide by adults of C. carnea at the recommended field dose had no significant effect on female fecundity, egg viability or adult longevity. Tebufenozide exhibited low toxicity towards the developmental stages of C. carnea and is therefore a candidate for inclusion in IPM strategies.

RESUMEN

Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound D-27 acting simultaneously on EcR and Ostrinia furnacalis chitinase (OfChtI). Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Ostrinia furnacalis larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, 6j, exhibited promising insecticidal activities against P. xylostella and S. frugiperda. Further protein binding assays and molecular docking indicated that 6j could target both EcR and OfChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs.

Asunto(s)

Diseño de Fármacos , Insectos , Insecticidas , Hormonas Juveniles , Animales , Quitinasas/antagonistas & inhibidores , Insecticidas/síntesis química , Insecticidas/química , Insecticidas/farmacología , Hormonas Juveniles/síntesis química , Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Simulación del Acoplamiento Molecular , Insectos/efectos de los fármacos , Insectos/crecimiento & desarrollo

RESUMEN

The indiscriminate application of synthetic pesticides on horticultural plants for the management of Bactrocera zonata has both economic and environmental implications due to the biomagnification of harmful residues in humans via the food chain. This necessitates the use of some eco-friendly control measures such as insect growth regulators (IGRs) as an alternative. A laboratory experiment was laid out to determine the potential chemosterilant effect of five IGRs including pyriproxyfen, novaluron, lufenuron, buprofezin, and flubendiamide at six different concentrations on B. zonata after treating adult diet. Using the oral bioassay, B. zonata were fed on IGRs impregnated diet (50-300 ppm/5 mL diet) which was replaced with the normal diet after 24 h of feeding. Ten pairs of B. zonata were placed in a separate plastic cage accommodating an ovipositor attractant guava for eggs collection and calculation. An analysis of the result revealed that fecundity and hatchability were higher at a low dose and vice versa. Lufenuron at 300 ppm/5 mL of diet significantly decreased the fecundity rate (31.1%) as compared to pyriproxyfen, novaluron, buprofezin and flubendiamide, which had 39.3%, 39.3%, 43.8%, and 47.5%, respectively. The lowest hatchability (19.9%) was noted in lufenuron treated diet followed by pyriproxyfen, novaluron, buprofezin, and flubendiamide, which had 22.1%, 25.0%, 30.9%, and 31.6%, respectively. Furthermore, in a population of crosses between the lufenuron treated male and female, a significant decrease in fecundity (45.5%) and hatchability (51.7%) was noted as compared to other IGRs. Overall, this study identified the chemosterilant potential of lufenuron on the population of B. zonata which can be integrated for its management strategy.

Asunto(s)

Hormonas Juveniles , Tephritidae , Animales , Humanos , Hormonas Juveniles/farmacología , Larva , Esterilizantes Químicos/farmacología

RESUMEN

Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI) characterized by bacterial biofilm formation and recalcitrance to immune-mediated clearance and antibiotics. The molecular events behind PJI infection are yet to be unraveled. In this sense, identification of polymorphisms in bacterial genomes may help to establish associations between sequence variants and the ability of S. aureus to cause PJI. Here, we report an experimental nucleotide-level survey specifically aimed at the intergenic regions (IGRs) of the icaADBCR locus, which is responsible for the synthesis of the biofilm exopolysaccharide PIA/PNAG, in a collection of strains sampled from PJI and wounds. IGRs of the icaADBCR locus were highly conserved and no PJI-specific SNPs were found. Moreover, polymorphisms in these IGRs did not significantly affect transcription of the icaADBC operon under in vitro laboratory conditions. In contrast, an SNP within the icaR coding region, resulting in a V176E change in the transcriptional repressor IcaR, led to a significant increase in icaADBC operon transcription and PIA/PNAG production and a reduction in S. aureus virulence in a Galleria mellonella infection model. In conclusion, SNPs in icaADBCR IGRs of S. aureus isolates from PJI are not associated with icaADBC expression, PIA/PNAG production and adaptation to PJI.

RESUMEN

BACKGROUND: Chrysoperla carnea (Neuroptera: Chrysopidae) is a voracious predator frequently used in biological control programs to suppress pest populations of economic importance. However, it performs its duty in a challenging environment where various stress factors such as non-target effects of insecticides limit expected outcomes. A study providing details of genetics, cross-resistance, realized heritability, and stability of insect growth regulators (IGRs) resistance such as pyriproxyfen in this bio-control agent is essential. RESULTS: Selection with pyriproxyfen, an IGR, resulted in 3092.10-fold and 39.60-fold resistance when judged against Susceptible and Field Pop, respectively. Very low cross-resistance to buprofezin while no cross-resistance to acetamiprid and spinosad was observed. Incompletely dominant, autosomal and polygenic resistance was also associated with high realized heritability (h2 = 0.35). Furthermore, resistance to pyriproxyfen was stable in this bio-control agent. CONCLUSION: These findings make Chrysoperla carnea an ideal fit in integrated pest management (IPM) programs where biological control approaches are employed in combination with IGRs sprays to control various insect pests especially Whitefly, Bemisia tabaci. Releasing pyriproxyfen-resistant Chrysoperla carnea in a multi-sprayed cropping environment would help to keep pest population below economic threshold level. It would also minimize risk of insecticide resistance development in pests surviving even after several insecticide applications. © 2020 Society of Chemical Industry.

Asunto(s)

Hemípteros , Insecticidas , Animales , Insectos/genética , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Piridinas/farmacología

RESUMEN

Synergistic effects of octopamine receptor agonists (OR agonists) have attracted many scientists based on their potent effects on mosquitoes. Herein, we determined the toxicity of selected insect growth regulators (IGRs) on fourth instar larvae of Culex quinquefasciatus. We evaluated the synergistic action of OR agonists on the toxicity of IGR insecticides to achieve a better understanding of their mode of action. As a result, pyriproxyfen was the most potent IGR insecticide (EC50 = 0.049 ng/ml) followed by lufenuron, novaluron, and diflubenzuron according to the IGR bioassay. Further, based on the acute bioassay, lufenuron was the most toxic IGR insecticide (LC50 = 44 ng/ml) after 24-h post treatment followed by pyriproxyfen, novaluron, and diflubenzuron (LC50 = 137, 263, and 1127 ng/ml, respectively). Similar tendency was observed after 48 and 72-h post treatment. Furthermore, OR agonists that combined with pyriproxyfen was the most significant effects after 48 and 72-h of exposure. The synergism with amitraz (AMZ) was more significant when co-treated with IGR insecticides compared to chlordimeform (CDM). These findings suggest that OR agonists are promising tools and are important alternative strategies as synergistic compounds in preventing and controlling Culex quinquefasciatus mosquitoes.

RESUMEN

The aim of this paper is to present further data for the validation of the Interpersonal Guilt Rating Scale-15 self-report (IGRS-15s; Gazzillo et al., 2018). We recruited a sample of 448 subjects, to whom we administered the IGRS-15s together with other empirically validated measures for the assessment of social desirability, shame, self-esteem, empathy, mental health and therapeutic alliance. In line with our hypotheses, the previously established three-factor structure of the IGRS-15s (Survivor guilt, Omnipotence guilt, and Self-hate) was confirmed. Moreover, the internal consistency and test-retest reliability of IGRS-15s were adequate to good. All the IGRS-15s factors were negatively correlated with self-esteem and mental health and positively correlated with shame; Survivor guilt and Omnipotence guilt were positively correlated with empathy; Survivor guilt and Self-hate negatively affected therapeutic alliance; and different traumas had different, theoretically predictable, impacts on the different kinds of guilt. Overall, these data support the reliability and validity of the IGRS-15s.

Asunto(s)

Empatía , Culpa , Autoimagen , Vergüenza , Encuestas y Cuestionarios/normas , Adulto , Femenino , Humanos , Relaciones Interpersonales , Masculino , Salud Mental , Reproducibilidad de los Resultados , Autoinforme

RESUMEN

This paper reports on a new species of the Baikal endemic sponge (fam. Lubomirskiidae) Swartschewskia khanaevi sp. nov. The description of this species is based on morphological and molecular data (ITS and mitochondrial IGRs). Morphologically, S. khanaevi sp. nov. differs from S. papyracea by loose tracts arranged in an irregular network as well as the presence on strongyles of compound spines looking like tubercles densely ornamented with simple spines. Moreover, specimens of S. khanaevi sp. nov. show a peculiar structure of the aquiferous system at the body surface that may be an adaptive trait for environmental conditions. Phylogenetic analysis has revealed that S. khanaevi sp. nov. forms a well-supported (0.99) monophyletic clade with S. papyracea and is allocated as its sister taxa.

RESUMEN

Fenoxycarb as a juvenile hormone analogue and methoxyfenozide (RH-2485) as a 20-hydroxyecdysone (20E) agonist are two main insect growth regulators (IGRs) used for pest control, whose insecticidal mechanisms had been widely reported in past decades. However, there were few studies focused on their effects on the carbohydrate metabolism of insects. Here, we reported that two IGRs (fenoxycarb and RH-2485) significantly affected growth and development of L. dispar larvae and caused larval lethality. Furthermore, both contens of three sugars (glycogen, threhalose, glucose) in four tissues (fat body, midgut, hemolymph and epidermis) and trehalase activity in three tissues (fat body, midgut and hemolymph) of L. dispar larvae were markedly affected by these two IGRs. Moreover, we found that mRNA expression levels of LdTPS, LdTre1 and LdTre2 in L. dispar larvae were dramatically suppressed by two IGRs. Additionally, chitin content in both midgut and epidermis decreased significantly after L. dispar larvae treated with fenoxycarb or RH-2485. Summarily, these results indicated that these two IGRs disturbed glycometabolism in L. dispar larvae, resulting in impeding chitin synthesis, generating new epidermis failure, disrupting molting and larval lethality in the end.

Asunto(s)

Quitina , Hormonas Juveniles , Animales , Hidrazinas , Larva , Fenilcarbamatos

RESUMEN

In the standard ISO soil toxicity test using Collembola, adult survival and juvenile production are the only endpoints that can be attainable. The information on egg production and egg hatching cannot be investigated in the ISO test. To overcome this limitation, in this study, the effects of teflubenzuron on life history parameters of Yuukianura szeptyckii (Collembola) were investigated with a compressed soil test. Teflubenzuron is an insect growth regulator and has a negative effect on egg production, and egg hatching process of arthropods. LC50 decreased with increases in exposure period from 6.97 mg/kg in the third week to 3.60 mg/kg in the fourth week. The EC50 for egg and juvenile production was 0.57 mg/kg and 0.26 mg/kg, respectively. The hatching rate decreased significantly from 46 to 7% as the concentration increased from 0.25 to 1.00 mg/kg, respectively, and the molting frequency was significantly affected only at > 4 mg/kg. The toxic contribution rate (TCR) was defined as the ratio of juvenile production at an exposure concentration compared with the control, and a simple life history model was developed for TCR estimations. At the lower concentrations (< 0.3 mg/kg), the hatching rate reduction was a main contributor to the total toxicity, but the adult mortality and egg production reduction were the main contributors at the higher concentrations (> 2.0 mg/kg). The contribution of egg production reduction remained relatively constant. Since collembolan populations in the soil can be composed of various developmental stages, the differences in the sensitivity to chemicals depending on the developmental stages should be included in the assessment of the toxic impact on soil ecosystems.

Asunto(s)

Benzamidas/toxicidad , Reproducción/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Animales , Artrópodos/efectos de los fármacos , Benzamidas/química , Ecosistema , Dosificación Letal Mediana , Suelo , Pruebas de Toxicidad

RESUMEN

Immature stages of the boll weevil, Anthonomus grandis grandis Boh. (Coleoptera: Curculionidae), develop protected inside cotton fruiting structures. Therefore, the adult beetles have become the main target of insecticide applications. The use of insect growth regulators (IGRs) is recommended against immatures, even though they may also affect the survival and reproductive traits of adult insects. The present study evaluated the impact of a juvenile hormone analog (pyriproxyfen), an ecdysteroid agonist (methoxyfenozide), and a chitin biosynthesis inhibitor (lufenuron) on adult cotton boll weevils, a key cotton pest. Mated and virgin beetles were treated by feeding them contaminated squares and cotton leaf discs that were previously immersed into pyriproxyfen, methoxyfenozide, and lufenuron solutions at field-rate concentrations. After exposure, treated couples were caged onto cotton plants, and survival, fecundity, and egg viability were evaluated. The IGRs neither affected the survival nor fecundity of adult boll weevils. On the other hand, egg viability was significantly reduced by lufenuron, regardless of whether the females were treated premating or postmating or whether their pairs were either treated or untreated. However, egg viability increased as the females aged since the initial exposure date to lufenuron, indicating a potential transovarial effect of this insecticide. Our results indicate that pyriproxyfen and methoxyfenozide do not affect adult boll weevils, whereas lufenuron temporarily reduces the egg viability of this key cotton pest.

Asunto(s)

Escarabajos , Insecticidas , Gorgojos , Animales , Femenino , Gossypium , Hormonas Juveniles , Reproducción

RESUMEN

Allatostatins (AST) are neuropeptides originally described as inhibitors of juvenile hormone (JH) synthesis in insects. Consequently, they have been considered as potential lead compounds for the discovery of new insect growth regulators (IGRs). In the present work, receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) was studied with 48 AST analogs, and a general approach for novel potent bioactive AST analogs is proposed. Hence, six novel AST analogs were designed and synthesized. Bioassays indicated that the majority novel analogs exhibited potent JH inhibitory activity, especially analog A6 (IC50: 3.79 nmol/L), which can be used as lead compound to develop new IGRs.

Asunto(s)

Proteínas de Insectos/química , Hormonas Juveniles/química , Neuropéptidos/química , Animales , Sitios de Unión , Cucarachas/química , Proteínas de Insectos/síntesis química , Proteínas de Insectos/metabolismo , Hormonas Juveniles/antagonistas & inhibidores , Hormonas Juveniles/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Neuropéptidos/síntesis química , Neuropéptidos/metabolismo , Unión Proteica , Relación Estructura-Actividad Cuantitativa , Receptores de Neuropéptido/química , Receptores de Neuropéptido/metabolismo

RESUMEN

The aim of this article is to present validation data about a self-report rating scale for the assessment of interpersonal guilt according to Control-Mastery Theory (CMT; Silbershatz, 2005; Weiss, 1993; Weiss, Sampson, & The Mount Zion Psychotherapy Research Group, 1986), the Interpersonal Guilt Rating Scale-15s (IGRS-15s). In order to perform the validation of this tool in an Italian sample we have collected a sample of 645 nonclinical subjects. They had to complete the IGRS-15s, the Scale for the Measurement of the Impending Punishment (SMIP; Caprara et al., 1990), the Interpersonal Guilt Questionnaire-67 (IGQ-67; O'Connor et al., 1997), the Psychological General Well-Being Index (PGWBI; Dupuy, 1984), and the Affective Neuroscience Personality Scales (ANPS; Davis, Panksepp, & Normansell, 2003), together with an ad-hoc questionnaire for collecting demographic data, the Socio-Demographical Schedule. We have performed a confirmatory factor analysis to verify if the four-factor solution based on CMT and replicated in previous research (Gazzillo et al., 2017) was confirmed. Then, we checked the retest reliability of IGRS-15s after four weeks in a random subsample of 54 subjects. In order to assess its concurrent and discriminant validity, we calculated the correlations between IGRS-15s assessment and SMIP and IGQ-67. Finally, to test its construct validity, we assessed the relationships between the IGRS-15s and the affective systems using the ANPS and the wellbeing assessed with the PGWBI. The data collected support the retest reliability and the concurrent and discriminant validity of the measure, and we have collected preliminary data about its construct validity. Examples of the possible clinical and research applications of this tool are discussed.

Asunto(s)

Culpa , Relaciones Interpersonales , Psicometría/métodos , Autoinforme , Adulto , Femenino , Humanos , Italia , Masculino , Escalas de Valoración Psiquiátrica , Reproducibilidad de los Resultados , Encuestas y Cuestionarios

RESUMEN

Nontranslated intergenic regions (IGRs) compose 10-15% of bacterial genomes, and contain many regulatory elements with key functions. Despite this, there are few systematic studies on the strength and direction of selection operating on IGRs in bacteria using whole-genome sequence data sets. Here we exploit representative whole-genome data sets from six diverse bacterial species: Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis, Salmonella enterica, Klebsiella pneumoniae, and Escherichia coli We compare patterns of selection operating on IGRs using two independent methods: the proportion of singleton mutations and the dI/dS ratio, where dI is the number of intergenic SNPs per intergenic site. We find that the strength of purifying selection operating over all intergenic sites is consistently intermediate between that operating on synonymous and nonsynonymous sites. Ribosome binding sites and noncoding RNAs tend to be under stronger selective constraint than promoters and Rho-independent terminators. Strikingly, a clear signal of purifying selection remains even when all these major categories of regulatory elements are excluded, and this constraint is highest immediately upstream of genes. While a paucity of variation means that the data for M. tuberculosis are more equivocal than for the other species, we find strong evidence for positive selection within promoters of this species. This points to a key adaptive role for regulatory changes in this important pathogen. Our study underlines the feasibility and utility of gauging the selective forces operating on bacterial IGRs from whole-genome sequence data, and suggests that our current understanding of the functionality of these sequences is far from complete.

Asunto(s)

ADN Intergénico/genética , Genoma Bacteriano , ARN no Traducido/genética , Secuencias Reguladoras de Ácidos Nucleicos , Secuencia Conservada/genética , Escherichia coli/genética , Evolución Molecular , Klebsiella pneumoniae/genética , Mycobacterium tuberculosis/genética , Ribosomas/genética , Salmonella enterica/genética , Staphylococcus aureus/genética , Streptococcus pneumoniae/genética

RESUMEN

Juvenile hormone (JH) analogs are nowadays in use to control harmful pests. In order to develop new bioactive molecules as potential pesticides, we have incorporated different active structural features like sulfonamide, aromatic rings, amide group, and amino acid moiety to the base structure. We have screened a series of designed novel JH analogs against JH receptor protein (jhbpGm-2RCK) of Galleria mellonella in comparison to commercial insect growth regulators (IGRs) - Pyriproxyfen (T1) and Fenoxycarb (T2). All analogs exhibit the binding energy profile comparable to commercial IGRs. Based upon these results, a series of sulfonamide-based JHAs (T3-T8) as IGRs have been synthesized and characterized. Further, the efficacy of synthesized analogs (T3-T8) and commercial IGRs (Pyriproxyfen and Fenoxycarb) has been assessed against fourth instars larvae of G. mellonella under the laboratory conditions. LC50 values of all the analogs (T1-T8) against the fourth instars larvae were 9.99, 10.12, 24.76, 30.73, 38.45, 34.15, 34.14, 19.48 ppm and the LC90 153.27, 131.69, 112.15, 191.46, 427.02, 167.13, 217.10, 172.00 ppm, respectively. Among these analogs, N-(1-isopropyl-2-oxo-3-aza-3-N-ethyl-pentanyl)-p-toluene sulfonamide (T8) and N-(1-isopropyl-2-oxo-3-aza-3-N-ethyl-pentanyl) benzene sulfonamide (T7) exhibited the good pest larval mortality at different exposure periods (in hours) and different concentrations (in ppm) in comparison to in use IGRs- T1 and T2. Bio assay results are supported by docking at higher concentration. The present investigation clearly exhibits that analog T8 could serve as a potential IGR in comparison to in use IGRs (T1 and T2). The results are promising and provide new array of synthetic chemicals that may be utilized as IGRs.

Asunto(s)

Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Modelos Moleculares , Conformación Molecular , Mariposas Nocturnas/efectos de los fármacos , Animales , Simulación por Computador , Enlace de Hidrógeno , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Fenotipo , Relación Estructura-Actividad

RESUMEN

The synergistic action of octopamine receptor agonists (OR agonists) on many insecticide classes (e.g., organophosphorus, pyrethroids, and neonicotinoids) on Aedes aegypti L. has been reported recently. An investigation of OR agonist's effect on insect growth regulators (IGRs) was undertaken to provide a better understanding of the mechanism of action. Based on the IGR bioassay, pyriproxyfen was the most potent IGR insecticide tested (EC50=0.0019ng/ml). However, the lethal toxicity results indicate that diafenthiuron was the most potent insecticide (LC50=56ng/cm(2)) on A. aegypti adults after 24h of exposure. The same trend was true after 48 and 72h of exposure. Further, the synergistic effects of OR agonists plus amitraz (AMZ) or chlordimeform (CDM) was significant on adults. Among the tested synergists, AMZ increased the potency of the selected IGRs on adults the greatest. As results, OR agonists were largely synergistic with the selected IGRs. OR agonists enhanced the lethal toxicity of IGRs, which is a valuable new tool in the field of A. aegypti control. However, further field experiments need to be done to understand the unique potential role of OR agonists and their synergistic action on IGRs.

Asunto(s)

Aedes/efectos de los fármacos , Dengue/prevención & control , Insectos Vectores/efectos de los fármacos , Hormonas Juveniles/toxicidad , Receptores de Amina Biogénica/agonistas , Animales , Bioensayo , Clorfenamidina/toxicidad , Sinergismo Farmacológico , Humanos , Insecticidas/clasificación , Insecticidas/toxicidad , Hormonas Juveniles/metabolismo , Larva/efectos de los fármacos , Control de Mosquitos/métodos , Sinergistas de Plaguicidas/toxicidad , Receptores de Amina Biogénica/efectos de los fármacos , Toluidinas/toxicidad

RESUMEN

Studying insecticide resistance in mosquitoes has attracted the attention of many scientists to elucidate the pathways of resistance development and to design novel strategies in order to prevent or minimize the spread and evolution of resistance. Here, we tested the synergistic action of piperonyl butoxide (PBO) and two octopamine receptor (OR) agonists, amitraz (AMZ) and chlordimeform (CDM) on selected novel insecticides to increase their lethal action on the fourth instar larvae of Aedes aegypti L. However, chlorfenapyr was the most toxic insecticide (LC50 = 193, 102, and 48 ng/ml, after 24, 48, and 72 h exposure, respectively) tested. Further, PBO synergized all insecticides and the most toxic combinatorial insecticide was nitenpyram even after 48 and 72 h exposure. In addition, OR agonists significantly synergized most of the selected insecticides especially after 48 and 72 h exposure. The results imply that the synergistic effects of amitraz are a promising approach in increasing the potency of certain insecticides in controlling the dengue vector Ae. aegypti mosquito.

Asunto(s)

Clorfenamidina/farmacología , Insecticidas/toxicidad , Sinergistas de Plaguicidas/farmacología , Butóxido de Piperonilo/farmacología , Receptores de Amina Biogénica/agonistas , Toluidinas/farmacología , Aedes/efectos de los fármacos , Animales , Dengue , Larva/efectos de los fármacos