The effects of somatic mutations on EGFR interaction with anti-EGFR monoclonal antibodies: Implication for acquired resistance

A number of mutations in the epidermal growth factor receptor (EGFR) have been identified that imparts resistance to anti-EGFR monoclonal antibodies (mAbs) in clinical and preclinical samples. Primary or acquired resistance to targeted therapy will eventually limit the clinical benefit of anticancer mAbs. The aim of the current study was to perform computational analysis to investigate the structural implications of the EGFR somatic mutations on its complexes with the four anti-EGFR mAbs (Cetuximab, Panitumumab, Necitumumab, and Matuzumab). Docking analysis and molecular dynamics (MD) simulations were performed to understand the plausible structural and dynamical implications caused by somatic mutations available in the Catalogue of Somatic Mutations in Cancer database on the EGFR and anti-EGFR mAbs. We found that EGFR^S492R and EGFR^V441I in complex with Cetuximab, EGFR^R377S and EGFR^S447Y in complex with Panitumumab, and EGFR^V441I in complex with Necitumumab have a weakest binding affinity in comparison to EGFR^WT in complex with the relevant mAb. Taken together with the results obtained from docking analysis and MD simulations, the present findings may suggest that, the S492R and V441I mutations confer resistance to Cetuximab, R377S and S447Y mutations mediate resistance to Panitumumab and finally, V441I mutation also confers resistance to Necitumumab.     

Effects of Nanoparticles on Activity of Lignan Biosynthesis Enzymes in Cell Suspension Culture of Linum usitatissimum L.

Russian Journal of Plant Physiology - Flax (Linum usitatissimum L.), as an important commercial crops, is a rich source of fatty acids, protein, dietary fiber and lignans. Flax plant has an...     

Prediction of the effect of chitosan on cell suspension culture of Azadirachta indica by response surface methodology

Plant Cell, Tissue and Organ Culture (PCTOC) - Azadirachta indica is used to insects repellent, control diabetes, and combat with cancer. In this study, the effect of different...     

Helicobacter pylori Omp18 and Its Application in Serologic Screening of Infection

Helicobacter pylori (Hp) is a major risk factor for gastrointestinal disorders including gastric cancer. We evaluated host serum antibody responses toward outer membrane protein18 in comparison with Urease A and B subunits. omp18 and ureA-ureB gene fragments were PCR amplified, cloned, and expressed in E. coli expression system. The expressed proteins were visualized on SDS-PAGE and confirmed by immuno-blotting. Purified proteins were applied in western blotting assays in comparison with local and foreign ELISA kits. ROC curve analysis identified the optimum cut-off points for each protein. rOmp18 represented the highest rates of sensitivity (94%), specificity (89%), PPV (97.4%), NPV (77.4%), and accuracy (93.2%) in comparison with urease A and B subunits. These immunologic indices were in ??substantial?? agreement (???=?0.7) with the gold standard tests for Hp detection. This study recommends Hp conserved Omp18 as a reliable serologic marker for accurate detection of Hp infection particularly for application in population screening approaches.     

Design of tissue culture media for efficient Prunus rootstock micropropagation using artificial intelligence models

Establishing optimized protocols for micropropagation of some economical plants, such as Prunus sp., is still one of the most important challenges for in vitro plant culture researchers. As an example, micropropagation of GF677 hybrid rootstocks (peach × almond) are extremely dependent on the medium ingredients and a large undesirable proportion of GF677 shoots need to be discarded as a result of hyperhydricity and chlorosis. In this study, an artificial intelligence technique—specifically neurofuzzy logic—has been employed, as a modeling tool, to increase knowledge on the effect of 8 ion macronutrients (NH₄ ⁺, NO₃ ^?, Ca²⁺, K⁺, Mg²⁺, SO₄ ^2?, PO₄ ^2? and Na⁺; as inputs) on three growth parameters (outputs): total number of shoots per explant, healthy number of shoots per explant, and their bud number. The model delivered new insights, by three sets of IF–THEN rules, pinpointing the key role of NO₃ ^? and their interactions (NO₃ ^? × Ca²⁺ and NO₃ ^? × Ca²⁺ × K⁺) on all growth parameters measured. All growth parameters showed a high correlation ratio between experimental and predicted values being 77.48, 91.78 and 90.78 for total shoots, healthy number and bud number, respectively. Regression coefficients higher than 77 % together with statistical significant ANOVA (p < 0.01) indicated good performance of neurofuzzy logic models. Moreover, The model also can be used for inferring the best combination of ion concentrations to obtain high quality GF677 micropropagated shoots. In conclusion, we assess the utility of neurofuzzy logic technology in modeling complex databases, identifying new complex interactions among macronutrients, and inferring new results and valuable knowledge, which can be applied to design new plant tissue culture media and improve plant micropropagation.     

Ethanol-inducible gene expression: first step towards a new green revolution?

The introduction of dwarf varieties of cereals was fundamental to the green revolution, but in the post-genomic era, the manipulation of plant morphology could be more sophisticated. A recent publication by Tahar Ait-ali et al. describes the use of the ethanol-inducible transgene expression system to re-examine plant architecture, and the genes that determine it. Their findings have implications for the manipulation of plant height and yield, and demonstrate the efficacy of regulated transgene expression for functional genomics.     

Effect of bovine viral diarrhoea virus biotypes on adherence of sperm to oocytes during in-vitro fertilization in cattle

Bovine viral diarrhoea virus (BVDV), a member of the Pestivirus genus, is one of the most important pathogens of dairy cattle; it can cause several clinical syndromes, ranging from subclinical to severe disease. The objectives of the current studies were to assess the effects of two biotypes of BVDV on sperm attachment to the zona pellucida (ZP) of oocytes and on fertilization rate in bovine in vitro fertilization (IVF). In two experiments, sperm at two concentrations (10⁵ and 10⁶/mL) and oocytes were incubated with 10⁶ TCID₅₀/mL cythopatic (CP) or noncythopatic (NCP) BVDV. In the first experiment, with the lower sperm concentration (10⁵/mL), male and female gametes were infected with CP or NCP BVDV, whereas in the second experiment, the sperm concentration was 10⁶/mL, and sperm and oocytes were also infected with CP or NCP BVDV. The number of sperm attached to the ZP and the fertilization rate were evaluated with fluorescence microscopy on the ZP of fertile and infertile oocytes. In the first experiment, compared to the control group (n = 97), oocytes infected with CP BVDV and incubated at the lower (10⁵/mL) sperm concentration positively affected sperm attachment (n = 123) to the ZP of fertile oocytes (P < 0.05). In comparison with the control group (n = 115), sperm infected with CP BVDV negatively affected sperm binding (n = 93) to the ZP of infertile oocytes (P < 0.05). In the second experiment (10⁶ sperm/mL), for both fertile and infertile oocyte groups, sperm attachment in the control group was very high and deemed uncountable. However, in treated groups, the number of sperm attached to the ZP was countable. Only sperm infected with CP BVDV negatively affected sperm binding capacity (n = 81) to the ZP of fertile oocytes (P < 0.05). Although CP and NCP BVDV significantly reduced the fertilization rate of oocytes incubated with a higher sperm concentration, with the lower sperm concentration, only NCP BVDV significantly diminished fertilization rate with contaminated sperm and oocytes (P < 0.05). In conclusion, this study supported the detrimental impacts of sperm or ooctyes infected with CP or NCP BVDV on sperm attachment to the ZP of bovine oocytes and on fertilization rate during bovine IVF.     

Helicobacter pylori bacterial ghost containing recombinant Omp18 as a putative vaccine

Helicobacter pylori bacterial ghosts, HPBG, were generated by PhiX174 mechanism and loaded with recombinant Omp18, which were then applied in therapeutic immunization of Hp-infected C57BL/6 mice. Recombinant Omp18 loaded HPBG plus cholera toxin stimulated serum anti-Hp and Omp18-specific antibodies which resulted in significant reduction of gastric Hp colonization (P < 0.05).