Dynamics of digging in wet soil

Numerous animals live in, and locomote through, subsea soils. To move in a medium dominated by frictional interactions, many of these animals have adopted unique burrowing strategies. This paper presents a burrowing model inspired by the Atlantic razor clam ({\it Ensis directus}), which uses deformations of its body to cyclically loosen and re-pack the surrounding soil in order to locally manipulate burrowing drag. The model reveals how an anisotropic body -- composed of a cylinder and sphere varying sinusoidally in size and relative displacement -- achieves unidirectional motion through a medium with variable frictional properties. This net displacement is attained even though the body kinematics are reciprocal and inertia of both the model organism and the surrounding medium are negligible. Our results indicate that body aspect ratio has a strong effect on burrowing velocity and efficiency, with a well-defined maximum for given kinematics and soil material properties

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

High-level expression and simplified purification of recombinant ricin A chain

Ricin toxin is a glycoprotein which catalytically inactivates eukaryotic ribosomes by depurination of a single adenosine residue from the 28S ribosomal RNA. The enzymatic activity is present in the A chain of the toxin molecule, whereas the B chain contains two binding sites for galactose. Since it is highly potent in inhibiting protein synthesis, the A chain is used to prepare cytotoxic conjugates effective against tumor cells. Such chimeric proteins are highly selective and have a wide range of clinical applications. Extensive preclinical studies on these conjugates require large amounts of purified A chain. Native ricin A chain is heterogeneous, since plants produce a number of isoforms of ricin toxin. Purified, native preparations often contain two types of ricin A chain which differ in the extent of glycosylation. By cloning and expressing the gene of A chain, one could obtain homogeneous toxin molecules devoid of carbohydrates. In addition, structural changes in the toxin polypeptide could be introduced by in vitro mutagenesis, which can improve the pharmacological properties and antitumor activity. Earlier methods of expression strategies using Escherichia coli have yielded only moderate levels of expression. In the present study, the coding region of ricin A chain was cloned into pET3b, a high-level expression vector under the control of the T7 promoter. Recombinant ricin A chain produced by this construct has an additional 14 amino acid residues at the NH 2 terminus. Subsequently, a NdeI site was created at the 5′ end of the gene by oligonucleotide-directed mutagenesis. The modified fragment was then introduced into pET3b vector to produce toxin polypeptide identical to the native sequence. The recombinant ricin A chain containing additional residues at the NH 2 terminus was, however, equally effective in inhibiting protein synthesis. This molecule also readily reassociated with the native B chain to produce whole ricin. In the present expression system, almost eightfold higher amounts of the recombinant protein were produced when compared to other constructs. Furthermore, modifications at the C-terminal end, such as the addition of pentalysine, did not affect the expression levels. This indicated that the expression system is suitable for producing mutant forms of ricin A chain as well. Finally, the purification scheme was simplified to obtain large amounts of pure toxin polypeptides

A Diphtheria Toxin-Interleukin 3 Fusion Protein is Cytotoxic to Primitive Acute Myeloid Leukemia Progenitors but Spares Normal Progenitors.

The relative cytotoxicity of a diphtheria toxin (DT) human interleukin 3(IL3) fusion protein (DT388IL3) was tested against primitive normal (n = 3)and acute myeloid leukemia (AML) progenitors (n = 7). After 24-h culture with 50 ng/ml DT388IL3, the mean percentages of kill of AML colony-forming cells (CFCs), long-term culture-initiating cells (LTC-ICs), and suspension culture-ICs (SC-ICs) were 82% (range, 47–100), 56% (range, 28–91), and 74% (range, 43–87), respectively, with most surviving progenitors being cytogenetically normal. Engraftment of DT388IL-3-treated AML cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice followed for 16 weeks was eradicated for two of these samples. In contrast, with normal bone marrow, mean percentages of CFC kill of 49 and 64% were seen with 50 or 250 ng/ml DT388IL3, respectively, whereas no significant kills were observed in the LTC-IC and SC-IC assays. The NOD/SCID mouse repopulating cell (RC) frequency in normal BM cells was also not reduced by DT388IL3 treatment. In subsequent experiments, NOD/SCID mice that received AML blasts i.v. followed in 24 h by 0.045 μg/g DT388IL3 daily i.p. × 5 showed mean percentages of reduction in AML engraftment of 83% (range, 14–100) and 57% (range, 0–98) after 4 and 12 weeks, respectively (n = 6). No evidence of leukemia was detected with two of six AML samples 12 weeks after one 5-day course of DT388IL3. Repeating the DT388IL3 treatment every 4 weeks enhanced its effectiveness against two additional samples. Thus, DT388IL3 kills primitive leukemic progenitors from a proportion of AML patients but shows no significant toxicity against equivalent normal cells