Identification of Ribonuclease Inhibitors for the Control of Pathogenic Bacteria

Funding Information: This work was funded by FCT\u2014Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia, I. P., through the projects MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020), and LS4FUTURE Associated Laboratory-LA/P/0087/2020. RGM was supported by an FCT contract (CEECIND/02065/2017: https://doi.org/10.54499/CEECIND/02065/2017/CP1428/CT0006). K.J.S. was supported by EU FP7 European Drug Initiative on Channels and Transporters (grant agreement ID: 201924). Publisher Copyright: © 2024 by the authors.Bacteria are known to be constantly adapting to become resistant to antibiotics. Currently, efficient antibacterial compounds are still available; however, it is only a matter of time until these compounds also become inefficient. Ribonucleases are the enzymes responsible for the maturation and degradation of RNA molecules, and many of them are essential for microbial survival. Members of the PNPase and RNase II families of exoribonucleases have been implicated in virulence in many pathogens and, as such, are valid targets for the development of new antibacterials. In this paper, we describe the use of virtual high-throughput screening (vHTS) to identify chemical compounds predicted to bind to the active sites within the known structures of RNase II and PNPase from Escherichia coli. The subsequent in vitro screening identified compounds that inhibited the activity of these exoribonucleases, with some also affecting cell viability, thereby providing proof of principle for utilizing the known structures of these enzymes in the pursuit of new antibacterials.publishe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Span effects on the static and dynamic response of low profile timber floors for Plywood Association of Australia

"This report describes test procedures followed to establish the static and dynamic response of a 3.6m wide x 7.2m long, two bay, timber framed, plywood sheathed Low Profile Floor (LPF) system. Timber framing was 190 x 45mm x F5 seasoned pine with 17mm thick x F11 tongue and grooved structural plywood glue/nailed to the top surfaces to provide the deck. Flanges glue/nailed to the underside of reinforced edge L and centre tee beam bearers were 120 x 35mm x F5 seasoned pine. The influence of span on structural response (both static and dynamic) has been investigated and some recommendations to control floor vibrations have been made. These recommendations are associated with limiting composite tee-beam bearer and joist stiffnesses to 1.5kN/mm and 0.75kN/mm respectively for spans up to and including 3.6m."--p. (i)

Wall racking tests on DUO-FAST nailed plywood sheathing to radiata pine framing for DUO-FAST, a division of Gangnail (Australia)

"This report presents the results of four wall racking tests performed on 50 x 45 mm x F8 radiata pine framing sheathed with 7 mm x F11 structural plywood interconnected by 2.5 mm diameter DUO-FAST fun-driven nails."--p. ii

Report on model panel racking tests to Australian Particleboard Research Institute

"This report presents the results obtained from eleven racking tests performed on 600 x 600 mm model panels to evaluate the suitability or otherwise of various particleboards as a sheathing media in dwelling construction. The panel frames were constructed of F8 Radiata Pine members 70 x 45 mm sheathed with 4 mm Fineline, 6 mm Texpan, 9 mm Texpan, 10 mm Pineboard, and 7 mm Radiata Pine plywood. A preliminary testing programme was implemented in which the sheathing was attached to the timber framiing members using nails at 75 and 38 mm centres. A final testing programme followed in which nail centres were expanded to 150 mm except for one test using 6 mm Texpan for which connection was effected by gluing using Araldite. Karri plywood sheathing was not available at the time of testing."--p. (i)

Proposal for the development of a "low profile" stressed skin timber floor : phase III - stage I

"This proposal outlines research to be performed in checking the "boundary conditions" associated with the load response of a 2.4 m wide x 4.8 m long, two bay timber floor system. Static and dynamic load response characteristics of a 3.6 m wide x 7.2 m long two bay system will also be investigated. As a third stage of the program, a floor using the 2.4 m and 3.6 m grid systems tested in the laboratory, will then be constructed on site at Capricornia Institue and tested under dynamic loading conditions. This floor will then form the basis of an "engineered experimental house".--p. i

Report on flexure tests of two scarf & butt jointed glulam beams for Wilson Hart & Co. Ltd., Maryborough

"This report briefly outlines the test procedure and presents the results of three point loading flexure tests carried out on two finger jointed glulam beams of dimensions 190 x 66 to determine their Modulus of Rupture (MOR), Modulus of Elasticity (MOE), and failure mode."--Summary

Phase II - stage I, engineered whole house : low profile floor - static and dynamic response of tee-beam bearer system

"This report discusses the influence of number of bays on static load response for the "panellised floor system" described in TWP Report No. 127. Additionally, the construction and static and dynamic serviceability limit states were examined for a continuous two-bay low profile floor system based on the new "tee-beam" bearer concept developed to combat the deficiencies of the panellised floor. The tee-beam bearer consists of a 100 x 45 mm web and 120 x 25 mm flange of F5 pine. The second moment of area (I) of the section closely approximates the double bearer of the panellised system. Plywood sheathing was 17 mm thick x F11 structural grade Radiata pine flooring glue/nailed to the timber framing members. One bay of the two bay continuous floor was loaded to its ultimate limit state by a simulated u.d. loading produced by one single 500 kN jack and a "whiffle-tree" arrangement loading sixteen nodes and two 50 kN jacks each loading two nodes."--p. iii

Low profile floor boundary bearer check under sustained load for Radiata Pine Research Institute in conjunction with Plywood Association of Australia

"This report gives results obtained from some short term static creep tests carried out on a Low Profile Floor (LPF) system. the floor was 2.4m wide and 4.8m long, being continuous over two bays. Timber framing members were F5 radiata pine and the sheathing 17mm thick F11 structural plywood. A special reinforced - L-edge bearer was included in the construction of the floor to accomodate long term dead loads from tiled roofs. A simulated roof load was applied to the edge bearer and also to a 200 x 75mm x F5 radiata pine bearer which, according to the Timber Framing Code would be necessary for the loading condition and 2.4mm span."--p. (i)

P.E.P. report 1983 to CIAE Council, Australian Particleboard Research Inst., Plywood Association of Australia

"This report documents discussions between the writer and timber engineering and wood science researchers at universities and research establishments in England, the United States of America and Canada during the overseas segment of his Professional Experience Programme (PEP). The report covers the section of the PEP from 8 July to 22 August during which time the period from 9 July to 18 July was spent in England, from 19 July to 13 August in the USA, and from 14 August to 20 August was spent in Canada. Discussions are presented chronologically in order of establishments visited."--p. (ii)