2001: A Mouse Genome Odyssey

A report on the 15th International Mouse Genome Conference, Edinburgh, UK, 21-24 October 2001

The role of coagulation on the fate of PFAS, brominated flame retardants and other trace contaminants in tertiary wastewater treatment for phosphorus control

Coagulant dosing to achieve low phosphorus concentrations in wastewater effluents may favour the removal of trace organics such as pharmaceuticals, plasticisers and flame retardants. Nevertheless, the behaviour of trace organics in coagulation processes is currently poorly understood because of the complex interactions between these compounds, the coagulants and dissolved organic matter (DOM). This study assessed the coagulation removal from synthetic secondary effluent of twenty-four compounds including ten PFAS and four brominated flame retardants. Testing involved two coagulants (alum, ferric chloride) and five DOM surrogates (resorcinol, benzoic acid, citric acid, tannic acid, humic acid); DOM surrogates had assorted molecular weights, structures, charges, and hydrophobicity. With coagulant doses of 14 mg Fe/L and 4 mg Al/L, ten trace organics were removed by >30 % in the presence of at least one DOM surrogate. Humic acid effected the highest removals owing to complexation of trace organics and subsequent co-removal by adsorption or sweep floc. For instance, removal extents for three brominated diphenyl ethers were 60 to 75 % with Al and 50 to 88 % with Fe (initial concentration 0.4 to 0.8 ng/L); PFTDA, a long-chain PFAS, was removed by 87 and 91 % with Fe in the presence of tannic or humic acid, respectively (initial concentration 0.03 μg/L). The varying coagulation performance of different treatment works in terms of trace substance removal can be explained because of the site-specific DOM characteristics. Addition of humic acids as complexing agents has the potential to improve the removal of hydrophobic trace substances, including some long-chain PFAS and brominated flame retardants

Fog2 is required for normal diaphragm and lung development in mice and humans

Congenital diaphragmatic hernia and other congenital diaphragmatic defects are associated with significant mortality and morbidity in neonates; however, the molecular basis of these developmental anomalies is unknown. In an analysis of E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic development. Fog2 (Zfpm2) maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de novo mutation resulting in a premature stop codon in a child who died on the first day of life secondary to severe bilateral pulmonary hypoplasia and an abnormally muscularized diaphragm. Using a phenotype-driven approach, we have established that Fog2 is required for normal diaphragm and lung development, a role that has not been previously appreciated. FOG2 is the first gene implicated in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and its necessity for pulmonary development validates the hypothesis that neonates with congenital diaphragmatic hernia may also have primary pulmonary developmental abnormalities

Barriers to women entrepreneurship. Different methods, different results?

Building on research by Akehurst et al. (Serv Ind J 32:2489-2505, 2012), this study analysed internal and external factors in women entrepreneurship and linked these factors to the barriers that women face when starting businesses. To do so, two contrasting statistical techniques were used: PLS and QCA. After analysing results from each of these techniques, we observed that family duties and difficulties in obtaining financing (both internal and external) were the main factors related to barriers faced by women entrepreneurs

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

Abstract 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

Segregation of seizure traits in C57 black mouse substrains using the repeated-flurothyl model.

Identifying the genetic basis of epilepsy in humans is difficult due to its complexity, thereby underlying the need for preclinical models with specific aspects of seizure susceptibility that are tractable to genetic analyses. In the repeated-flurothyl model, mice are given 8 flurothyl-induced seizures, once per day (the induction phase), followed by a 28-day rest period (incubation phase) and final flurothyl challenge. This paradigm allows for the tracking of multiple phenotypes including: initial generalized seizure threshold, decreases in generalized seizure threshold with repeated flurothyl exposures, and changes in the complexity of seizures over time. Given the responses we previously reported in C57BL/6J mice, we analyzed substrains of the C57BL lineage to determine if any of these phenotypes segregated in these substrains. We found that the generalized seizure thresholds of C57BL/10SNJ and C57BL/10J mice were similar to C57BL/6J mice, whereas C57BL/6NJ and C57BLKS/J mice showed lower generalized seizure thresholds. In addition, C57BL/6J mice had the largest decreases in generalized seizure thresholds over the induction phase, while the other substrains were less pronounced. Notably, we observed only clonic seizures during the induction phase in all substrains, but when rechallenged with flurothyl after a 28-day incubation phase, ∼80% of C57BL/6J and 25% of C57BL/10SNJ and C57BL/10J mice expressed more complex seizures with tonic manifestations with none of the C57BL/6NJ and C57BLKS/J mice having complex seizures with tonic manifestations. These data indicate that while closely related, the C57BL lineage has significant diversity in aspects of epilepsy that are genetically controlled. Such differences further highlight the importance of genetic background in assessing the effects of targeted deletions of genes in preclinical epilepsy models