Target Resistance of Eleusine indica to Glyphosate

[Objectives]This study was conducted to detect the evolution of resistance to glyphosate in Eleusine indica.[Methods]In the previous study,glyphosate-resistant population T2-4 was screened out from E.indica populations in sugarcane fields in Guangxi.In this study,we determined the resistance index of T2-4 by whole plant bioactivity assay and further explored the molecular biological mechanism of resistance.[Results]The resistance index of T2-4 was 112,and it is thus a highly resistant population.Amino acid mutations were found at positions 102,106 and 381 in the EPSPS sequence of T2-4,containing at least a triple mutation allele in Thr-102-Ile,Pro-106-Ser and Pro-381-Leu and a double mutation allele in Pro-106-Ser and Pro-381-Leu.qPCR was used to determine the EPSPS gene copy number and expression in resistant plants of T2-4.EPSPS gene copy number and expression both increased,with 8.3-fold higher copy number and 2.7-fold higher expression than the sensitive population.Therefore,the resistance of T2-4 to glyphosate was mainly caused by multiple target mechanisms including mutation of EPSPS gene,copy number increase and expression increase,and the resistance of E.indica to glyphosate needs our high attention.[Conclusions]At present,the level of resistance to glyphosate is very high in the sugarcane fields of Guangxi,and it is necessary to take a variety of weed control measures to solve the problem of glyphosate resistance.

Constitutive modelling of concrete material subjected to low-velocity projectile impact:insights into damage mechanism and target resistance

This paper presents a numerical study to improve the understanding of the complex subject of penetration and perforation of concrete targets impacted by low-velocity projectiles.The main focus is on the damage mechanisms and the major factors that account for the target resistance of the concrete.An improved continuous surface cap model recently proposed was employed.The model was first equipped with element erosion criteria and was adequately validated by comparisons with ballistic experiments.Comprehensive numerical simulations were carried out where the individual influence of tensile,shear,and volumetric behaviors(pore collapse)of a concrete target on its ballistic performance was investigated.Results demonstrated that cratering on the front face and scabbing on the rear face of the concrete target were mainly dominated by its tensile behavior.The major target resistance came from the second tunneling stage which was primarily governed by the shear and volumetric behaviors of the concrete.Particularly,this study captured the pore collapse-induced damage phenomenon during the high-pressure tunneling stage,which has been extensively reported in experiments but has usually been neglected in previous numerical investigations.

MicroRNA-216a: a potential therapeutic target for drug resistance and recurrent of liver cancer

The Editor welcomes submissions for possible publication in the Letters to the Editor section.Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published.Authors of the article being commented on will be given an opportunity to offer a timely response to the letter.Authors of letters will be notified that the letter has been received.Unpublished letters cannot be returned.

Dormancy of Amaranthus retroflexus L. Seeds and Physiological Response Seedlings to Acifluorfen Sodium

Amaranthus retroflexus L. is a serious and widespread malignant weed in soybean fields in Heilongjiang Province. Exploring the dormancy characteristics of A. retroflexus L. seeds and the physiological response of its seedlings to acifluorfen sodium can provide a basis for further researches on its resistance mechanism. Using newly harvested and stored A. retroflexus L. seeds for one year as experimental materials, the effects of different concentrations of HCl, NaOH, water temperature, gibberellic acid(GA) and polyethylene glycol(PEG) on the dormancy and germination of A. retroflexus L. seeds were studied. The sensitivity of A. retroflexus L.to acifluorfen sodium was determined using bioassay. The effects on leaf chlorophyll content and target enzyme activity were studied at a normal dosage of 360 g a.i. hm^(-2) and a doubling dosage of 720 g a.i. hm^(-2) of acifluorfen sodium. Newly harvested seeds exhibiting dormancy were soaked in water of various temperatures and in different concentrations of NaOH and HCl, which were ineffective in breaking the seed dormancy. GA could break seed dormancy, and the highest seed germination rate reached 93.33% when they were soaked at 3 000 mg·L^(-1) for 72 h and 4 000 mg·L^(-1) for 48 h. The drought stress was simulated with a 15%-25% polyethylene glycol solution, which had no significant effect on the seed germination rate. The GR_(50) value of acifluorfen sodium for A. retroflexus L. was 705.7 g a.i. hm^(-2), which was 1.96 times the recommended dose in the field. After the application of different doses of acifluorfen sodium, the chlorophyll content of A. retroflexus L. reached its minimum value 3 days after treatment(DAT), and then gradually increased. The activity of the target enzyme protoporphyrinogen oxidase(PPO) reached the highest value at 7 DAT under different dosages, and gradually returned to normal levels thereafter. Soaking with gibberellin was an effective method to break seed dormancy. A. retroflexus L. seeds had certain drought resistance during the germination process. A. retroflexus L. was not sensitive to acifluorfen sodium and acifluorfen sodium ether, and could not effectively inhibit the PPO activity, indicating that A. retroflexus L. had target resistance to acifluorfen sodium.

An overview of resistance to Human epidermal growth factor receptor 2(Her2)targeted therapies in breast cancer

Breast cancer(BC)is the second most common cause of cancer-related deaths and the most frequently diagnosed cancer in females.Among breast cancer types,HER2-positive breast cancer occurs in nearly 20%of human breast cancers and is associated with increased aggressiveness,poor prognosis,and shortened overall survival.HER2+breast cancer is currently managed with multidisciplinary treatment strategies including surgery,radiation,chemotherapy,and targeted therapy.Drug resistance remains a continuing challenge,especially to targeted therapy utilizing monoclonal antibodies and tyrosine kinase inhibitors.This review discusses some of the recent molecular mechanisms that are involved in the development of resistance to Her2-targeted therapies including the PI3K/Akt/mTOR pathway,IGF-IR,Src,c-MET,the PP2A family,CD36,p27^(kip1),and miRNAs.

Targeting mitochondrial biogenesis for preventing and treating insulin resistance in diabetes and obesity:Hope from natural mitochondrial nutrients

Insulin resistance is an important feature of type 2 diabetes and obesity. The underlying mechanisms of insulin resistance are still unclear. Mitochondrial dysfunction,

Mutant epidermal growth factor receptor contributes to head and neck cancer growth and resistance to EGFR targeting

Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous-cell carcinoma (HNSCC) and its expression levels correlate with decreased patient survival. Nonetheless, therapies aiming at blocking EGFR has shown limited efficacy in a proportion of patients with HNSCC in clinical trials. Sok et al. in a recent paper (Clin Cancer Res, 2006, 12:5064-5073 ) attempted to ascertain whether it is due to mutation of EGFR. As the most common form of mutation of EGFR seen in several other types of cancer is a truncation mutation,

Knockin of the G275E mutation of the nicotinic acetylcholine receptor (nAChR) α6 confers high levels of resistance to spinosyns in Spodoptera exigua

Spinosyns,including spinosad and spinetoram,act on the insect central nervous system,gradually paralyzing or destroying the target insect.Spinosad resistance is associated with loss-of-function mutations in the nicotinic acetylcholine receptor(nAChR)α6 subunit in a number of agricultural pests.Using gene editing,nAChRα6 has been verified as a target for spinosyns in five insect species.Recently,a point mutation(G275E)in exon 9 of nAChRα6 was identified in spinosad-resistant strains of Thrips palmi and Tuta absoluta.To date,no in vivo functional evidence has been obtained to support that this mutation is involved in spinosyn resistance in lepidopteran pests.In this study,the G275E mutation was introduced into the nAChR of Spodoptera exigua using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology.Reverse transcriptase-polymerase chain reaction and sequencing confirmed that this mutation was present in exon 9 of the nAChR transcripts in the edited 275E strain.The results of bioassays showed that the 275E strain was highly resistant to spinosad(230-fold)and spinetoram(792-fold)compared to the unedited background strain,directly confirming that the G275E mutation of the nAChRα6 subunit confers high levels of spinosyn resistance in S.exigua.Inheritance analysis showed that the resistance trait is autosomal and incompletely recessive.This study employs a reverse genetics approach to validate the functional role played by the G275E mutation in nAChRα6 of S.exigua in spinosyns resistance and provides another example of the use of CRISPR/Cas9 gene-editing technology to confirm the role played by candidate target site mutations in insecticide resistance.

Estimation of load and resistance factors using the thirdmoment method based on the 3P-Iognormal distribution

Load and resistance factors are generally obtained using the first order reliability method(FORM)in which the design point should be determined and derivative-based iterations used.In this article,the thirdmoment reliability index,based on the three-parameter lognormal(3P-lognormal)distribution,is investigated.A simple method based on the third-moment method for estimating load and resistance factors is then proposed,and a simple formula for the target mean resistance is also presented to avoid iterative computations.Unlike the currently used method,the proposed method can be used to determine load and resistance factors,even when the probability density functions(PDFs)of the basic random variables are not available.Moreover,the proposed method does not require the iterative computation of derivatives or any design points.Thus,the method provides a more convenient and effective way to estimate load and resistance factors in practical engineering applications.Numerical examples are presented to demonstrate the advantages of the proposed third moment method for determining load and resistance factors.

Molecular mechanisms of enzalutamide resistance in prostate cancer

An estimated 30,000 men in the United States will die of metastatic prostate cancer(PCa)each year due to the development of therapy resistance,most notably resistance to second-generation antiandrogen enzalutamide.The vast majority of PCa is driven by the androgen receptor(AR).Enzalutamide is an AR antagonist,which extends patient survival and is widely used in the clinic for the treatment of castration-resistant prostate cancer(CRPC);however,many patients will have primary or develop acquired resistance and continue to progress.Characterization of the molecular mechanisms of enzalutamide resistance provides insight into potentially efficacious therapies for enzalutamide-resistant CRPC(ER-CRPC).Understanding these mechanisms is critical for the identification of biomarkers predictive of therapy resistance and the development of therapeutic strategies to target ER-CRPC.