Bilateral hip arthroplasty: is 1-week staging the optimum strategy?

Seventy-nine patients underwent bilateral hip arthroplasty staged either at 1 week (Group 1) or after greater intervals (as suggested by the patients, mean 44 weeks, range 16-88 weeks) (Group 2), over a five year period at one Institution. Sixty-eight patients (29 bilateral hip resurfacings and 39 total hip replacements) completed questionnaires regarding their post-operative recovery, complications and overall satisfaction with the staging of their surgery

Recognition of extended linear and cyclised polyketide mimics by a Type II acyl carrier protein

Extended linear and cyclised polyketide mimics were synthesized and high-resolution solution NMR structures were used to probe the interactions of the actinorhodin polyketide ACP with these surrogates.</p

In silico analyses of maleidride biosynthetic gene clusters

Maleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the ‘core’ set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel putative maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS 125634. We have undertaken phylogenetic analyses and comparative bioinformatics on all known and putative maleidride biosynthetic gene clusters to gain further insights regarding these unique biosynthetic pathways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40694-022-00132-z

Deconstructing density: strategic dilemmas confronting the post-Apartheid city

Public authorities in many countries around the world are seeking to raise urban densities. Residential densification is particularly important in South Africa because of the colonial and apartheid legacy of sprawling, fragmented, racially divided cities. The paper examines the case for densifying central Cape Town and provides a framework to help deconstruct the concept and explore the policy challenges faced. It focuses on the bold aim to treble the area’s population within 10 years, and identifies issues where further consideration and public debate are required for how this can be achieved in a way that is desirable, affordable and fair. A key message is the need to understand both the composition of demand for central city living and the challenges involved in supplying suitable housing and amenities at higher densities. The level of social inequality in the city poses greater complications than elsewhere

Maleidride biosynthesis – construction of dimeric anhydrides – more than just heads or tails

Covering: up to early 2022 Maleidrides are a family of polyketide-based dimeric natural products isolated from fungi. Many maleidrides possess significant bioactivities, making them attractive pharmaceutical or agrochemical lead compounds. Their unusual biosynthetic pathways have fascinated scientists for decades, with recent advances in our bioinformatic and enzymatic understanding providing further insights into their construction. However, many intriguing questions remain, including exactly how the enzymatic dimerisation, which creates the diverse core structure of the maleidrides, is controlled. This review will explore the literature from the initial isolation of maleidride compounds in the 1930s, through the first full structural elucidation in the 1960s, to the most recent in vivo, in vitro, and in silico analyses

Core steps to the Azaphilone family of fungal natural products

Azaphilones are a family of polyketide-based fungal natural products that exhibit interesting and useful bioactivities. This minireview explores the literature on various characterised azaphilone biosynthetic pathways, which allows for a proposed consensus scheme for the production of the core azaphilone structure, as well as identifying early diversification steps during azaphilone biosynthesis. A consensus understanding of the core enzymatic steps towards a particular family of fungal natural products can aid in genome-mining experiments. Genome mining for novel fungal natural products is a powerful technique for both exploring chemical space and providing new insights into fungal natural product pathways

Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis

Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins. Ring cycle: The enzymes involved in the cyclization of the maleidride family of bioactive fungal natural products, including agnestadride A and byssochlamic acid, were identified. These previously unknown proteins show homology to ketosteroid isomerases (KI-like) and phosphatidylethanolamine-binding proteins (PEBP-like).BBSRCSyngent

Report of the Advisory Committee in Seismology

The Advisory Committee in Seismology has pleasure in reporting the continued progress of its study of California earth movements during the year 1924-1925 without essential change of plan. A considerable amount of geologic work in the study of fault zones has been done during the year in the Mojave Desert and in Death Valley, the system of primary triangulation for the detection and measurement of horizontal displacements has progressed rapidly and effectively, and the development of suitable instruments for determining the two horizontal components of local earth movements has progressed to completion. Ground for a new laboratory has been purchased by the California Institute of Technology and the construction of the central station laboratory building upon it has been begun. The laboratory is expected to be occupied by Mr. H. O. Wood, Research Associate in Seismology, and his associates, about January 1, 1926. It is hoped that additional stations will also be occupied before the close of the present calendar year (1925), and that actual work in what has been happily termed the seismologic triangulation of California will be successfully inaugurated

Novel nonadride, heptadride and maleic acid metabolites from the byssochlamic acid producer <i>Byssochlamys fulva </i>IMI 40021 – an insight into the biosynthesis of maleidrides

The filamentous fungus Byssochlamys fulva strain IMI 40021 produces (+)-byssochlamic acid 1, its novel dihydroanalogue 2 and four related secondarymetabolites. Agnestadrides A, 17 and B, 18 constitute a novel class of seven-membered ring, maleic anhydride-containing (hence termed heptadride) natural products. The putative maleic anhydride precursor 5 for both nonadride and heptadride biosynthesis was isolated as a fermentation product for the first time and its structure confirmed by synthesis. Acid 5 undergoes facile decarboxylation to anhydride 6. The generic term maleidrides is proposed to encompass biosynthetically-related compounds containing maleic anhydride moieties fused to an alicyclic ring, varying in size and substituents