Obituary: Arthur Cruickshank 1932 - 2011. A native Gondwanan, who studied the former continent's fossil tetrapods

Dr Arthur Richard Ivor Cruickshank died on 4th December 2011, aged 79, in the Borders General Hospital, Melrose, Scotland. Arthur Cruickshank was part of the post-war generation of palaeontologists who laid the foundations on which today’s researchers build. Appropriately for someone from an expatriate Scots family living in Kenya, much of his work was on the extinct reptiles of the great southern palaeocontinent of Gondwana

Application of digital particle image velocimetry to insect aerodynamics: measurement of the leading-edge vortex and near wake of a Hawkmoth.

Some insects use leading-edge vortices to generate high lift forces, as has been inferred from qualitative smoke visualisations of the flow around their wings. Here we present the first Digital Particle Image Velocimetry (DPIV) data and quantitative analysis of an insect’s leading-edge vortex and near wake at two flight speeds. This allows us to describe objectively 2D slices through the flow field of a tethered Tobacco Hawkmoth (Manduca sexta). The near-field vortex wake appears to braodly resemble elliptical vortex loops. The presence of a leading-edge vortex towards the end of the downstroke is found to coincide with peak upward force production measured by a six-component force–moment balance. The topology of Manduca’s leading-edge vortex differs from that previously described because late in the downstroke, the structure extends continuously from wingtip across the thorax to the other wingtip

Multimodal computational colonoscopy

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Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes

Heme a is an essential cofactor for function of cytochrome c oxidase in the mitochondrial electron transport chain. Several evolutionarily conserved enzymes have been implicated in the biosynthesis of heme a, including the heme a synthase Cox15. However, the structure of Cox15 is unknown, its enzymatic mechanism and the role of active site residues remain debated, and recent discoveries suggest additional chaperone-like roles for this enzyme. Here, we investigated Cox15 in the model eukaryote Saccharomyces cerevisiae via several approaches to examine its oligomeric states and determine the effects of active site and human pathogenic mutations. Our results indicate that Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Four conserved histidine residues are demonstrated to be critical for eukaryotic heme a synthase activity and cannot be substituted with other heme-ligating amino acids. The 20-residue linker region connecting the two conserved domains of Cox15 is also important; removal of this linker impairs both Cox15 multimerization and enzymatic activity. Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme. Structural modeling of Cox15 suggests these two mutations affect protein folding and heme binding, respectively. We conclude that Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase

Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes

Heme a is an essential cofactor for function of cytochrome c oxidase in the mitochondrial electron transport chain. Several evolutionarily conserved enzymes have been implicated in the biosynthesis of heme a, including the heme a synthase Cox15. However, the structure of Cox15 is unknown, its enzymatic mechanism and the role of active site residues remain debated, and recent discoveries suggest additional chaperone-like roles for this enzyme. Here, we investigated Cox15 in the model eukaryote Saccharomyces cerevisiae via several approaches to examine its oligomeric states and determine the effects of active site and human pathogenic mutations. Our results indicate that Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Four conserved histidine residues are demonstrated to be critical for eukaryotic heme a synthase activity and cannot be substituted with other heme-ligating amino acids. The 20-residue linker region connecting the two conserved domains of Cox15 is also important; removal of this linker impairs both Cox15 multimerization and enzymatic activity. Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme. Structural modeling of Cox15 suggests these two mutations affect protein folding and heme binding, respectively. We conclude that Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase

The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase Assembly

Heme a is an essential metalloporphyrin cofactor of the mitochondrial respiratory enzyme cytochrome c oxidase (CcO). Its synthesis from heme b requires several enzymes, including the evolutionarily conserved heme a synthase (Cox15). Oligomerization of Cox15 appears to be important for the process of heme a biosynthesis and transfer to maturing CcO. However, the details of this process remain elusive, and the roles of any additional CcO assembly factors that may be involved remain unclear. Here we report the systematic analysis of one such uncharacterized assembly factor, Pet117, and demonstrate in Saccharomyces cerevisiae that this evolutionarily conserved protein is necessary for Cox15 oligomerization and function. Pet117 is shown to reside in the mitochondrial matrix, where it is associated with the inner membrane. Pet117 functions at the later maturation stages of the core CcO subunit Cox1 that precede Cox1 hemylation. Pet117 also physically interacts with Cox15 and specifically mediates the stability of Cox15 oligomeric complexes. This Cox15-Pet117 interaction observed by co-immunoprecipitation persists in the absence of heme a synthase activity, is dependent upon Cox1 synthesis and early maturation steps, and is further dependent upon the presence of the matrix-exposed, unstructured linker region of Cox15 needed for Cox15 oligomerization, suggesting that this region mediates the interaction or that the interaction is lost when Cox15 is unable to oligomerize. Based on these findings, it was concluded that Pet117 mediates coupling of heme a synthesis to the CcO assembly process in eukaryotes

Waste Gasification

This document summarizes the work the IGT Team has conducted on the topic of waste to energy gasification over the Cal Poly Winter, Spring, and Fall quarters of 2019. The project is being carried out by four Cal Poly Mechanical Engineering students: Nash Taylor, Glyn Lewis, David McCallum, and Nicholas Ordonez and the sponsor of this project is Tod duBois. The team’s original goal was to successfully create a system that compiles residential solid waste on a small scale, gasifies it, and measures the typical syngas outputs, so that the team may assess the viability of gasification of household waste on a small scale. The project has drastically changed multiple times and the changes have been documented throughout this paper. Due to safety concerns and uncertainty regarding the prototype vessel, the team’s final goal is to prove successful gasification using their keg based system. The team has spent most of the quarters conducting researching and narrowing the scope of work to something they believe they can successfully and manageably complete over the next year. The purpose of this document is to summarize the research, present and justify some design choices, and present the design solution as resolved to the current date

Small molecule screening in zebrafish: an in vivo approach to identifying new chemical tools and drug leads

In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification