Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Synthesis of some thiazolidinones and 5-oxoimidazolines as biologically potent agents

628-6314-Aminobe nzophenone 1 on condensation with different aralclehydes yield schiff's bases 2a-o which on cyclization with mercapto acetic acid afford the corresponding 4-(5'H-2'aryl-4'thiazolidinon-3'-yl)-benzophenones 3a-<b style="mso-bidi-font-weight: normal">o. While cyclocondensation of 1 with various azlactones yield 4-(4'-aryl idene-2'-phenyl- 5'-oxo-imidazolin-1'-yl )benzophenones 4a-m. The structure of the compounds have been confirmed from elemental analysis, IR , 1H NMR and mass spectral data. All the compounds have been evaluated in vitro for antimicrobial and antimycobacterial activities.</span

Synthesis of pyrazolines and cyanopyridines as potential antimicrobial agents

57-613,3'-Bis-(4-acetophenylaminosulphonyl)benzophcnone 1 on condensation with various aldehydes yields chalcones 2a-p which on cyclization with hydrazine hydrate and malononitrile furnishes the corresponding 3,3'-bis-(5-aryl-1 H/acetyl-pyrazolin- 3-yl-4-phenylaminosulphonyl)benzophenones 3a-p,3'a-p and 3,3'-bis-(2-amino-3-cyano-4-aryl pyridin-6-yl-4-phenylaminosulphonyl)benzophenones 4a-p. The structure of the compounds have been confirmed from elemental analyses, IR, 1H NMR and mass spectral data. All the products have been evaluated for their in vitro growth inhibitory activity against different microbes

A synthesis of some new 2-azetidinones as potential antitubercular agents

716-7182-Amino-4-(α-methoxyiminocarbmethoxymethyl) thiazole 1 on condensation with different aromatic aldehydes furnishes Schiff bases 2a-o which on treatment with chloroacetyl chloride in the presence of triethylamine as basic catalyst afford 2-azetidinones 3a-o. The synthesised compounds 3a-o have been tested in vitro for their antitubercular activity against Mycobacterium tuberculosis H37Rv.</i

Use of RAPD marker to confirm mutation in morphological variants on Neem tree

Neem (Azadirachta indica A. Juss.) is commercially valuable medicinal plant studied for molecular analysis. In the present study, a morphological variant of neem was observed near our department. The leaf pattern was abnormal (crimpled or curly) morphologically observed and was against normal leaves. This curly leaves containing neem tree considered as mutant against normal. It was considered as either environmental/ chemical influence or certain variation that might lead to mutation in plant genome. To confirm mutation, in this experimentation, this morphological analysis was confirmed by molecular analysis. For that, the genomic DNA was extracted from both the plants and subjected to RAPD analysis. The morphological variants were shown distinct variation in DNA pattern by selected primers. Thus, RAPD profile proves that there was mutation in plant genome. This result supports the initiative to utilize morphological variants in plant breeding applications, and DNA fingerprinting

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Generation of HIV-1 based bi-cistronic lentiviral vectors for stable gene expression and live cell imaging.</span>

669-676The study of protein-protein interactions, protein localization, protein organization into higher order structures and organelle dynamics in live cells, has greatly enhanced the understanding of various cellular processes. Live cell imaging experiments employ plasmid or viral vectors to express the protein/proteins of interest fused to a fluorescent protein. Unlike plasmid vectors, lentiviral vectors can be introduced into both dividing and non dividing cells, can be pseudotyped to infect a broad or narrow range of cells, and can be used to generate transgenic animals. However, the currently available lentiviral vectors are limited by the choice of fluorescent protein tag, choice of restriction enzyme sites in the Multiple Cloning Sites (MCS) and promoter choice for gene expression. In this report, HIV-1 based bi-cistronic lentiviral vectors have been generated that drive the expression of multiple fluorescent tags (EGFP, mCherry, ECFP, EYFP and dsRed), <span style="mso-bidi-font-weight: bold">using two different promoters. The presence of a unique MCS with multiple restriction sites allows the generation of fusion proteins with the fluorescent tag of choice, allowing analysis of multiple fusion proteins in live cell imaging experiments. These novel lentiviral vectors are improved delivery vehicles for gene transfer applications and are important tools for live cell imaging in vivo. </span

Use of Telemedicine for Post-discharge Assessment of the Surgical Wound: International Cohort Study, and Systematic Review with Meta-analysis

Objective: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardised assessment tools are needed. Summary background data: Surgical site infection is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery. Methods: The primary outcome of this study was surgical site infection reported up to 30-days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analysed primary data from an international cohort study of adult patients undergoing abdominal surgery who were discharged from hospital before 30-days after surgery. The second part combined this data with the results of a systematic review to perform a meta-analysis of all available data conducted in accordance with PRIMSA guidelines (PROSPERO:192596). Results: The cohort study included 15,358 patients from 66 countries (8069 high, 4448 middle, 1744 low income). Of these, 6907 (45.0%) were followed up using telemedicine. The SSI rate reported using telemedicine was slightly lower than with in-person follow-up (13.4% vs. 11.1%, P&lt;0.001), which persisted after risk adjustment in a mixed-effects model (adjusted odds ratio: 0.73, 95% confidence interval 0.63-0.84, P&lt;0.001). This association was consistent across sensitivity and subgroup analyses, including a propensity-score matched model. In nine eligible non-randomised studies identified, a pooled mean of 64% of patients underwent telemedicine follow-up. Upon meta-analysis, the SSI rate reported was lower with telemedicine (odds ratio: 0.67, 0.47-0.94) than in-person (reference) follow-up (I2=0.45, P=0.12), although there a high risk of bias in included studies. Conclusions: Use of telemedicine to assess the surgical wound post-discharge is feasible, but risks underreporting of SSI. Standardised tools for remote assessment of SSI must be evaluated and adopted as telemedicine is upscaled globally