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Multichannel system for recording myocardial electrical activity
Published in Waldemar Wójcik, Sergii Pavlov, Maksat Kalimoldayev, Information Technology in Medical Diagnostics II, 2019
O. Vlasenko, O. Chaikovska, I. Rokunets, O. Vlasenko, W. Wójcik, S.V. Pavlov, A. Bazarbayeva
The proposed electrophysiological complex with floating multichannel electrode allows fast, efficient and cheap evaluation of myocardial condition during pharmacological intervention. The technique was validated on the standard pharmacological drugs with well-known action mechanism. Field potentials from intact heart were recorded and the key myocardial parameters were calculated and analysed. Using this technique, the myocardial profile can be assessed at preclinical stage of novel drug development, during the action of any other factors—electrical, chemical, genetic, etc. Also, this technique could be used in parallel recordings at different organs and systems of organs in one animal.
George Wells Beadle (1903–1981)
Published in Krishna Dronamraju, A Century of Geneticists, 2018
The highly stimulating environment at Caltech greatly helped Beadle’s career. The faculty and associates then included Morgan, Sturtevant, Bridges, Dobzhansky, Schultz, Anderson, Emerson (son of R.A. Emerson), Belar, and the Lindegrens. Among the numerous visitors, Beadle (1974) recalled Haldane, Darlington, and Karpechenko. It was precisely during his visit to Caltech that Haldane deeply influenced Beadle’s thinking about biochemical genetics (see Kay 1989). The extensive program of research on the chemical genetics of anthocyanins under Haldane’s direction at the John Innes Institution in England was in full swing at that time. In several personal conversations and seminars, Haldane discussed the results with Beadle and others at Caltech (Beadle 1974, Kay 1989, Scott-Moncrieff 1981). Beadle, who had just completed his graduate work, was infected by Haldane’s enthusiasm and excitement in biochemical genetics. Shortly afterward, Beadle visited Haldane at the John Innes Institution in England.
Gendering ‘good' and ‘bad' genes
Published in Kate Reed, Gender and Genetics, 2012
Since the emergence of the Human Genome project in the 1980s we have witnessed great advances in the new genetics. The aim of the Genome Project was to find the chemical genetic base for the 4000 or so genetic diseases that affect humans, as well as to identify genetic links with diseases in the hope of creating new preventions and cures (Conrad 1997). Through the emergence and development of the genome project we have been able to make great advances in science and medicine through the identification and subsequent screening of a number of genes from the BRCA1 gene, to Huntingdon’s disease and cystic fibrosis. However, while there may be benefits to such developments in genetics sociologists have raised a number of concerns. As Conrad and Gabe (1999) sargue while the new genetics is more medical, involves individual choice and has not led to overtly state policies, the pall of eugenic history is reflected in anxieties about genetics. Duster (1990) for example has raised concerns over the discriminatory nature of the selective screening practices for inherited genetic disorders specifically distributed by race and ethnicity. Duster (1990) does not suggest that we are back to the open and malevolent forms of eugenics, but rather suggests that we may have eugenics by the back door in the name of health through screens, treatments and therapies.
Advances in preclinical approaches to Chagas disease drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Fernando Villalta, Girish Rachakonda
Chemical genomics was used to identify cytochrome b as a novel drug target for Chagas Disease [78]. It was found that the compound GNF7686 targets cytochrome b, a component of the mitochondrial electron transport chain crucial for ATP generation. GNF7686 is a potent inhibitor of T. cruzi growth in vitro. This study provides new insights into the use of chemical genetics with biochemical target validation to the discovery of additional novel drug targets and drug leads for Chagas disease.
Novel antiviral drug discovery strategies to tackle drug-resistant mutants of influenza virus strains
Published in Expert Opinion on Drug Discovery, 2019
Influenza virus genome replication and transcription occurs in the host cell nucleus, and therefore, the nuclear trafficking of RdRp provides an important avenue for the inhibition of viral replication as previously described in section 3.1. A major function of influenza NP involves the nuclear and cytoplasmic trafficking of vRNP complexes, which differs from the function of NP in other non-segmented or segmented (-) RNA viruses [104]. Importantly, NP is an integral part of the viral RNA complex (vRNPs) and provides a target independent of the polymerase complex (PB1, PB2, PA) (Section 3.1.1.) for anti-influenza drugs. Kao et al. reported the first small molecule that was shown to inhibit the function of NP in 2010 [105]. Using a forward chemical genetics approach and a library containing more than 50,000 compounds, they selected 39 compounds for further mode of action studies. They then focused on NP nuclear trafficking using fluorescence microscopy and selected five compounds, the most effective of which had anti-influenza virus activity with an EC50 < 1 µM as measured by plaque reduction assay. The commercially available compound nucleozin (Table 6) was identified based on structural information, and further mode of action studies showed that the compound triggers NP aggregation and inhibits NP nuclear localization (Stage 4 in Figure 1). Krystal et al. identified an analog of nucleozin, with a simple OMe substitution (compound 3, Table 6), that was almost threefold more potent than nucleozin [106]. This analog induced the formation of NP oligomers, as confirmed by dynamic light scattering analysis and by X-ray co-crystal structure of the analog. Further modification of the nucleozin resulted in identification of compound 5 (Table 5) with increased potency. There are three genera of influenza viruses (A, B and C types), as classified by antigenic differences in NP and the matrix protein. Hence, the direct targeting of NP was successful only with compounds active against IAVs.