Withdrawal notice to "Structural and functional characterization for interaction of silver nanoparticles with ergostrol in Trichoderma harzianum" [Microb. Pathog. 125 (2018) 318-324].

This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error. The full Elsevier Policy on Article Withdrawal can be found at (https://www.elsevier.com/about/policies/article-withdrawal).

Diverse Resistance Mechanisms to the Third-Generation ALK Inhibitor Lorlatinib in ALK-Rearranged Lung Cancer.

PURPOSE: Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with proven efficacy in patients with ALK-rearranged lung cancer previously treated with first- and second-generation ALK inhibitors. Beside compound mutations in the ALK kinase domain, other resistance mechanisms driving lorlatinib resistance remain unknown. We aimed to characterize the mechanisms of resistance to lorlatinib occurring in patients with ALK-rearranged lung cancer and design new therapeutic strategies in this setting. EXPERIMENTAL DESIGN: Resistance mechanisms were investigated in 5 patients resistant to lorlatinib. Longitudinal tumor biopsies were studied using high-throughput next-generation sequencing. Patient-derived models were developed to characterize the acquired resistance mechanisms, and Ba/F3 cell mutants were generated to study the effect of novel ALK compound mutations. Drug combinatory strategies were evaluated in vitro and in vivo to overcome lorlatinib resistance. RESULTS: Diverse biological mechanisms leading to lorlatinib resistance were identified. Epithelial-mesenchymal transition (EMT) mediated resistance in two patient-derived cell lines and was susceptible to dual SRC and ALK inhibition. We characterized three ALK kinase domain compound mutations occurring in patients, L1196M/D1203N, F1174L/G1202R, and C1156Y/G1269A, with differential susceptibility to ALK inhibition by lorlatinib. We identified a novel bypass mechanism of resistance caused by NF2 loss-of-function mutations, conferring sensitivity to treatment with mTOR inhibitors. CONCLUSIONS: This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression.

Transcriptomic Analysis With the Progress of Symbiosis in 'Crack-Entry' Legume Arachis hypogaea Highlights Its Contrast With 'Infection Thread' Adapted Legumes.

In root-nodule symbiosis, rhizobial invasion and nodule organogenesis is host controlled. In most legumes, rhizobia enter through infection threads and nodule primordium in the cortex is induced from a distance. But in dalbergoid legumes like Arachis hypogaea, rhizobia directly invade cortical cells through epidermal cracks to generate the primordia. Herein, we report the transcriptional dynamics with the progress of symbiosis in A. hypogaea at 1 day postinfection (dpi) (invasion), 4 dpi (nodule primordia), 8 dpi (spread of infection in nodule-like structure), 12 dpi (immature nodules containing rod-shaped rhizobia), and 21 dpi (mature nodules with spherical symbiosomes). Expression of putative ortholog of symbiotic genes in 'crack entry' legume A. hypogaea was compared with infection thread-adapted model legumes. The contrasting features were i) higher expression of receptors like LYR3 and EPR3 as compared with canonical Nod factor receptors, ii) late induction of transcription factors like NIN and NSP2 and constitutive high expression of ERF1, EIN2, bHLH476, and iii) induction of divergent pathogenesis-responsive PR-1 genes. Additionally, symbiotic orthologs of SymCRK, ROP6, RR9, SEN1, and DNF2 were not detectable and microsynteny analysis indicated the absence of a RPG homolog in diploid parental genomes of A. hypogaea. The implications are discussed and a molecular framework that guides crack-entry symbiosis in A. hypogaea is proposed.

Structural and functional characterization for interaction of silver nanoparticles with ergostrol in Trichoderma harzianum.

Silver ions, because of its recognised antimicrobial activity are reported in several regions for the very long time while ergosterol, apart from its role as a secondary metabolite, structural component of the fungal cell membranes, also turns out to be activating defence response in plants. Silver ions biosynthesized by terpene ergosterol producing Trichoderma harzianum could be used against other plant pathogenic fungi. In this work, possible interaction of the silver ions with ergosterol enzyme has been investigated using a computational approach. Protein model construction via prior knowledge of sequences and molecular ligand docking experiments as well as structural and sequence comparisons were executed to identify potential active-site in ergosterol enzyme. Moldock score of -48.5747 with the reranking score of -40.0228 has been reported by Molegro Virtual Docker(MVD) at ergosterol enzyme's active site positions for silver ion. Apart from the core of the active site, four other positions have been occupied by silver ion. The interacting site surrounded by Cys339, Arg343, Lue365, Leu336 and Trp371 formed hydrophobic bonds with silver. The anti-microbial activity against phytopathogens is believed to increase synergistically when combined with ergosterol enzyme. Thus the computational analysis of silver ion in conjugation with ergosterol enzyme provided additional strategies to improve the ability of the Trichoderma strains in biocontrol of pathogenic fungi. In the present study, silver ion based formulations which are produced by strong bio-control fungi as shown were estimated in response to different plant pathogen in further studies.

Detection of Replication Origin Sites in Herpesvirus Genomes by Clustering and Scoring of Palindromes with Quadratic Entropy Measures.

Replication in herpesvirus genomes is a major concern of public health as they multiply rapidly during the lytic phase of infection that cause maximum damage to the host cells. Earlier research has established that sites of replication origin are dominated by high concentration of rare palindrome sequences of DNA. Computational methods are devised based on scoring to determine the concentration of palindromes. In this paper, we propose both extraction and localization of rare palindromes in an automated manner. Discrete Cosine Transform (DCT-II), a widely recognized image compression algorithm is utilized here to extract palindromic sequences based on their reverse complimentary symmetry property of existence. We formulate a novel approach to localize the rare palindrome clusters by devising a Minimum Quadratic Entropy (MQE) measure based on the Renyi's Quadratic Entropy (RQE) function. Experimental results over a large number of herpesvirus genomes show that the RQE based scoring of rare palindromes have higher order of sensitivity, and lesser false alarm in detecting concentration of rare palindromes and thereby sites of replication origin.

Schematic for efficient computation of GC, GC3, and AT3 bias spectra of genome.

Selection of synonymous codons for an amino acid is biased in protein translation process. This biased selection causes repetition of synonymous codons in structural parts of genome that stands for high N/3 peaks in DNA spectrum. Period-3 spectral property is utilized here to produce a 3-phase network model based on polyphase filterbank concepts for derivation of codon bias spectra (CBS). Modification of parameters in this model can produce GC, GC3, and AT3 bias spectra. Complete schematic in LabVIEW platform is presented here for efficient and parallel computation of GC, GC3, and AT3 bias spectra of genomes alongwith results of CBS patterns. We have performed the correlation coefficient analysis of GC, GC3, and AT3 bias spectra with codon bias patterns of CBS for biological and statistical significance of this model.