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handbook of water and wastewater microbiology
\"Access to safe water is a fundamental human need and therefore a basic human right\" --Kofi Annan, United Nations Secretary GeneralEdited by two world-renowned scientists in the field, The Handbook of Water and Wastewater Microbiology provides a definitive and comprehensive coverage of water and wastewater microbiology.
eBook
Landscapes of privilege
James and Nancy Duncan look at how the aesthetics of physical landscapes are fully enmeshed in producing the American class system. Focusing on an archetypal upper class American suburb-Bedford in Westchester County, NY-they show how the physical presentation of a place carries with it a range of markers of inclusion and exclusion.
James Duncan is a University Lecturer in Geography at Cambridge University, and Nancy Duncan is Affiliated Lecturer of Geography at Cambridge University.
eBook
Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients
Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49–14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8 + T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08–18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 –a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Journal Article
Quantifying the potential scale of mitigation deterrence from greenhouse gas removal techniques
Greenhouse gas removal (GGR) techniques appear to offer hopes of balancing limited global carbon budgets by removing substantial amounts of greenhouse gases from the atmosphere later this century. This hope rests on an assumption that GGR will largely supplement emissions reduction. The paper reviews the expectations of GGR implied by integrated assessment modelling, categorizes ways in which delivery or promises of GGR might instead deter or delay emissions reduction, and offers a preliminary estimate of the possible extent of three such forms of ‘mitigation deterrence’. Type 1 is described as ‘substitution and failure’: an estimated 50–229 Gt-C (or 70% of expected GGR) may substitute for emissions otherwise reduced, yet may not be delivered (as a result of political, economic or technical shortcomings, or subsequent leakage or diversion of captured carbon into short-term utilization). Type 2, described as ‘rebounds’, encompasses rebounds, multipliers, and side-effects, such as those arising from land-use change, or use of captured CO2 in enhanced oil recovery. A partial estimate suggests that this could add 25–134 Gt-C to unabated emissions. Type 3, described as ‘imagined offsets’, is estimated to affect 17–27% of the emissions reductions required, reducing abatement by a further 182–297 Gt-C. The combined effect of these unanticipated net additions of CO2 to the atmosphere is equivalent to an additional temperature rise of up to 1.4 °C. The paper concludes that such a risk merits further deeper analysis and serious consideration of measures which might limit the occurrence and extent of mitigation deterrence.
Journal Article
Screening and characterization of a diverse panel of metagenomic imine reductases for biocatalytic reductive amination
Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities.High-throughput biocatalytic screening and metagenomics have been used to discover over 300 imine reductases (IREDs) and subsequently produce a sequence-diverse panel of IREDs suitable for optimizing the synthesis of chiral amines. Additional characterization identified biocatalysts that accommodate structurally demanding amines and ketones for enzymatic reductive aminations.
Journal Article