Gridshell as Formwork: Proof of Concept for a New Technique for Constructing Thin Concrete Shells Supported by Gridshell as Formwork

This paper documents an empirical experiment conducted in August 2014 as proof of concept for a new method of constructing concrete shells. An idea initially presented by the first author in 2012, it uses redeployable gridshells onto which fabric is midstressed and concrete applied. Primarily, this system addresses key issues that led to their decline in use: construction methods/formwork systems were not reusable, nor were they easily customizable to create different shapes. Employing 27 man-hours over seven days, two concrete shells were achieved using the same reusable and reconfigurable formwork. Lightweight (0.6 kg) PVC gridshell formwork supported 106.92 kg of concrete to create a concrete shell that covered 1.11 m2 (floor area). The construction verifies a low-cost (£6.06/m2) efficiency and material utilization in the construction of very strong wide-spanning thin concrete structures. Detailed analysis of formwork behavior during construction and detailed measurements of resultant shell results prove this new method of deployable gridshells as a reusable and reconfigurable formwork to construct very strong concrete shells very quickly. Whilst the emphasis of the research focused on the construction process, the vaults were tested and sustained a failure load of 4.2 kN (4.32 times their deadweight), applied as a point load at the crown

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

Catalytic cleavage of HEAT and subsequent covalent binding of the tetralone moiety by the SARS-CoV-2 main protease

Here we present the crystal structure of SARS-CoV-2 main protease (Mpro) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization of Mpro with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in the framework of a large X-ray crystallographic screening project of Mpro against a drug repurposing library, consisting of 5632 approved drugs or compounds in clinical phase trials. Further investigations showed that HEAT is cleaved by Mpro in an E1cB-like reaction mechanism into 2-methylene-1-tetralone and tyramine. The catalytic Cys145 subsequently binds covalently in a Michael addition to the methylene carbon atom of 2-methylene-1-tetralone. According to this postulated model HEAT is acting in a pro-drug-like fashion. It is metabolized by Mpro, followed by covalent binding of one metabolite to the active site. The structure of the covalent adduct elucidated in this study opens up a new path for developing non-peptidic inhibitors

Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes.

Fruiting bodies (sporocarps, sporophores or basidiomata) of mushroom-forming fungi ( Agaricomycetes) are among the most complex structures produced by fungi. Unlike vegetative hyphae, fruiting bodies grow determinately and follow a genetically encoded developmental program that orchestrates their growth, tissue differentiation and sexual sporulation. In spite of more than a century of research, our understanding of the molecular details of fruiting body morphogenesis is still limited and a general synthesis on the genetics of this complex process is lacking. In this paper, we aim at a comprehensive identification of conserved genes related to fruiting body morphogenesis and distil novel functional hypotheses for functionally poorly characterised ones. As a result of this analysis, we report 921 conserved developmentally expressed gene families, only a few dozens of which have previously been reported to be involved in fruiting body development. Based on literature data, conserved expression patterns and functional annotations, we provide hypotheses on the potential role of these gene families in fruiting body development, yielding the most complete description of molecular processes in fruiting body morphogenesis to date. We discuss genes related to the initiation of fruiting, differentiation, growth, cell surface and cell wall, defence, transcriptional regulation as well as signal transduction. Based on these data we derive a general model of fruiting body development, which includes an early, proliferative phase that is mostly concerned with laying out the mushroom body plan (via cell division and differentiation), and a second phase of growth via cell expansion as well as meiotic events and sporulation. Altogether, our discussions cover 1 480 genes of Coprinopsis cinerea, and their orthologs in Agaricus bisporus, Cyclocybe aegerita, Armillaria ostoyae, Auriculariopsis ampla, Laccaria bicolor, Lentinula edodes, Lentinus tigrinus, Mycena kentingensis, Phanerochaete chrysosporium, Pleurotus ostreatus, and Schizophyllum commune, providing functional hypotheses for ~10 % of genes in the genomes of these species. Although experimental evidence for the role of these genes will need to be established in the future, our data provide a roadmap for guiding functional analyses of fruiting related genes in the Agaricomycetes. We anticipate that the gene compendium presented here, combined with developments in functional genomics approaches will contribute to uncovering the genetic bases of one of the most spectacular multicellular developmental processes in fungi. Citation: Nagy LG, Vonk PJ, Künzler M, Földi C, Virágh M, Ohm RA, Hennicke F, Bálint B, Csernetics Á, Hegedüs B, Hou Z, Liu XB, Nan S, M. Pareek M, Sahu N, Szathmári B, Varga T, Wu W, Yang X, Merényi Z (2023). Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes. Studies in Mycology 104: 1-85. doi: 10.3114/sim.2022.104.01

Hemosporidian blood parasites in seabirds—a comparative genetic study of species from Antarctic to tropical habitats

Whereas some bird species are heavily affected by blood parasites in the wild, others reportedly are not. Seabirds, in particular, are often free from blood parasites, even in the presence of potential vectors. By means of polymerase chain reaction, we amplified a DNA fragment from the cytochrome b gene to detect parasites of the genera Plasmodium, Leucocytozoon, and Haemoproteus in 14 seabird species, ranging from Antarctica to the tropical Indian Ocean. We did not detect parasites in 11 of these species, including one Antarctic, four subantarctic, two temperate, and four tropical species. On the other hand, two subantarctic species, thin-billed prions Pachyptila belcheri and dolphin gulls Larus scoresbii, were found infected. One of 28 thin-billed prions had a Plasmodium infection whose DNA sequence was identical to lineage P22 of Plasmodium relictum, and one of 20 dolphin gulls was infected with a Haemoproteus lineage which appears phylogenetically clustered with parasites species isolated from passeriform birds such as Haemoproteus lanii, Haemoproteus magnus, Haemoproteus fringillae, Haemoproteus sylvae, Haemoproteus payevskyi, and Haemoproteus belopolskyi. In addition, we found a high parasite prevalence in a single tropical species, the Christmas Island frigatebird Fregata andrewsi, where 56% of sampled adults were infected with Haemoproteus. The latter formed a monophyletic group that includes a Haemoproteus line from Eastern Asian black-tailed gulls Larus crassirostris. Our results are in agreement with those showing that (a) seabirds are poor in hemosporidians and (b) latitude could be a determining factor to predict the presence of hemosporidians in birds. However, further studies should explore the relative importance of extrinsic and intrinsic factors on parasite prevalence, in particular using phylogenetically controlled comparative analyses, systematic sampling and screening of vectors, and within-species comparisons

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M^(pro)), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M^(pro). In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2

X ray screening identifies active site and allosteric inhibitors of SARS CoV 2 main protease

The coronavirus disease COVID 19 caused by SARS CoV 2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID 19, we have performed a high throughput x ray crystallographic screen of two repurposing drug libraries against the SARS CoV 2 main protease Mpro , which is essential for viral replication. In contrast to commonly applied x ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS CoV