DOCU-CLIM: A global documentary climate dataset for climate reconstructions.

Documentary climate data describe evidence of past climate arising from predominantly written historical documents such as diaries, chronicles, newspapers, or logbooks. Over the past decades, historians and climatologists have generated numerous document-based time series of local and regional climates. However, a global dataset of documentary climate time series has never been compiled, and documentary data are rarely used in large-scale climate reconstructions. Here, we present the first global multi-variable collection of documentary climate records. The dataset DOCU-CLIM comprises 621 time series (both published and hitherto unpublished) providing information on historical variations in temperature, precipitation, and wind regime. The series are evaluated by formulating proxy forward models (i.e., predicting the documentary observations from climate fields) in an overlapping period. Results show strong correlations, particularly for the temperature-sensitive series. Correlations are somewhat lower for precipitation-sensitive series. Overall, we ascribe considerable potential to documentary records as climate data, especially in regions and seasons not well represented by early instrumental data and palaeoclimate proxies.

Building back better from COVID-19: Knowledge, emergence and social contracts.

COVID-19 recovery is an opportunity to enhance life chances by Building Back Better, an objective promoted by the UN and deployed politically at national level. To help understand emergent and intentional opportunities to Build Back Better, we propose a research agenda drawing from geographical thinking on social contracts, assemblage theory and the politics of knowledge. This points research towards the ways in which everyday and professional knowledge cocreation constrains vision and action. Whose knowledge is legitimate, how legitimacy is ascribed and the place of science, the media and government in these processes become sites for progressive Building Back Better.

The role of gender in peer-group perceptions of climate scientists' media statements.

This research explores whether environmental scientists perceive their male and female peers differently when making statements in the media including policy advocacy. Environmental scientists in the United Kingdom were provided with a media statement by a fictitious scientist containing a mixture of scientific information and advocacy, and asked to rate the statement against various attributes. Attributes were designed to represent stereotypes associated with male and female tendencies, and with science (impartial objectivity) and the media (dramatic narrative). The statements were randomly assigned to one of two male and two female scientists. Where the statements were attributed to a female scientist, male environmental scientists rated the fictitious scientist as significantly more 'dramatic' and 'biased' than their female counterparts did. These gendered attributes are typically held as contrary to the norms of science, suggesting an implicit bias among male scientists when reviewing their female peers' media statements.

Carbohydrate scaffolds as glycosyltransferase inhibitors with in vivo antibacterial activity.

The rapid rise of multi-drug-resistant bacteria is a global healthcare crisis, and new antibiotics are urgently required, especially those with modes of action that have low-resistance potential. One promising lead is the liposaccharide antibiotic moenomycin that inhibits bacterial glycosyltransferases, which are essential for peptidoglycan polymerization, while displaying a low rate of resistance. Unfortunately, the lipophilicity of moenomycin leads to unfavourable pharmacokinetic properties that render it unsuitable for systemic administration. In this study, we show that using moenomycin and other glycosyltransferase inhibitors as templates, we were able to synthesize compound libraries based on novel pyranose scaffold chemistry, with moenomycin-like activity, but with improved drug-like properties. The novel compounds exhibit in vitro inhibition comparable to moenomycin, with low toxicity and good efficacy in several in vivo models of infection. This approach based on non-planar carbohydrate scaffolds provides a new opportunity to develop new antibiotics with low propensity for resistance induction.

A versatile synthetic approach toward diversity libraries using monosaccharide scaffolds.

The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build on 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied on glucose and allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations on a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics.

Critical pathway analysis to determine key uncertainties in net impacts on disease burden in Bangladesh of arsenic mitigation involving the substitution of arsenic bearing for groundwater drinking water supplies.

It has been increasingly recognised that calculation of the disease burden due to populations, such as in Bangladesh, extensively using hazardous arsenic bearing well waters, must explicitly account for the trade-off between diarrhoeal disease incidence and that of arsenic-related diseases. This is because it is likely that moves to alternative drinking water sources, be they surface waters or even more distant groundwaters, without further mitigation would result in a concurrent increase in diarrhoeal disease. In this paper, we update the model of Lokuge of the effects of such arsenic mitigation on disease burden in Bangladesh, using updated population data and background disease estimates. We run a critical pathway analysis on the model using Standardised Mortality Ratios (SMRs) for diabetes mellitus and ischemic heart disease from different epidemiological studies recently reviewed by Navas-Acien. Our analysis agrees with that of Lokuge that mitigation simply involving the substitution of a range of surface waters for well water sources with As > 50 microg/L would have a net positive impact on disease burden, as determined by deaths and Disability Life Adjusted Years (DALYs). In contrast, however, there is considerable ambiguity in the analogous results for mitigation for all the population exposed to well water with As > 10 microg/L. Depending upon the data source chosen for diabetes mellitus and ischaemic heart disease SMRs, such mitigation is modelled to have either a positive or a negative net impact on overall disease burden. The modelled negative impacts are entirely commensurate with the rationale for seeking groundwater as an alternative to surface waters as a drinking water supply, and highlight the practical requirement for multiple mitigation strategies, including those directed at ensuring the microbiological safety and continued protection of any alternative water supplies. Our study highlights the need for (i) adequate epidemiological studies involving multiple exposure categories, ideally resulting in an accurate dose-response relationship for arsenic uptake and the non-malignant high incidence conditions diabetes mellitus and ischemic heart disease for individuals with the socioeconomic and nutritional status of the Bangladeshi populations, and (ii) refined estimates of the diarrhoel disease burden arising from usage of surface waters.

Effects of 17-alkyl-16,17-dihydrogibberellin A(5) derivatives on growth and flowering in Lolium temulentum.

Several gibberellins in which the 16-methyl group of the 16-epimers of dihydro-GA(5) had been replaced by ethyl, n-propyl and n-butyl were prepared and tested at doses of 1, 5 or 25&mgr;g per plant for their effects on stem growth and flowering of the grass Lolium temulentum. The ethyl and n-propyl derivatives were most inhibitory of elongation, the exo-isomers being more active than the endo-forms. While both isomers of dihydro-GA(5) promoted flowering, among the 17-alkyl analogues, only the exo-ethyl derivative showed significant activity.