Demystifying academics to enhance university-business collaborations in environmental science

In countries globally there is intense political interest in fostering effective university-business collaborations, but there has been scant attention devoted to exactly how an individual scientist's workload (i.e. specified tasks) and incentive structures (i.e. assessment criteria) may act as a key barrier to this. To investigate this an original, empirical dataset is derived from UK job specifications and promotion criteria, which distil universities' varied drivers into requirements upon academics. This work reveals the nature of the severe challenge posed by a heavily time-constrained culture; specifically, tension exists between opportunities presented by working with business and non-optional duties (e.g. administration and teaching). Thus, to justify the time to work with business, such work must inspire curiosity and facilitate future novel science in order to mitigate its conflict with the overriding imperative for academics to publish. It must also provide evidence of real-world changes (i.e. impact), and ideally other reportable outcomes (e.g. official status as a business' advisor), to feed back into the scientist's performance appraisals. Indicatively, amid 20-50 key duties, typical full-time scientists may be able to free up to 0.5 day per week for work with business. Thus specific, pragmatic actions, including short-term and time-efficient steps, are proposed in a "user guide"to help initiate and nurture a long-term collaboration between an early- to mid-career environmental scientist and a practitioner in the insurance sector. These actions are mapped back to a tailored typology of impact and a newly created representative set of appraisal criteria to explain how they may be effective, mutually beneficial and overcome barriers. Throughout, the focus is on environmental science, with illustrative detail provided through the example of natural hazard risk modelling in the insurance sector. However, a new conceptual model of academics' behaviour is developed, fusing perspectives from literature on academics' motivations and performance assessment, which we propose is internationally applicable and transferable between sectors. Sector-specific details (e.g. list of relevant impacts and user guide) may serve as templates for how people may act differently to work more effectively together

C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays

Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit these residue differences between the histone substrate binding sites in order to improve affinity for the KDM4-subfamily over KDM5-subfamily enzymes. In particular, residues E169 and V313 (KDM4A numbering) were targeted. Additionally, the conformational restriction of the flexible pyridopyrimidinone C8-substituent was investigated. These approaches yielded potent and cell-penetrant dual KDM4/5-subfamily inhibitors including 19a (KDM4A and KDM5B Ki = 0.004 and 0.007 μM, respectively). Compound cellular profiling in two orthogonal target engagement assays revealed a significant reduction from biochemical to cell-based activity across multiple analogues; this decrease was shown to be consistent with 2OG competition, and suggest that sub-nanomolar biochemical potency will be required with C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one compounds to achieve sub-micromolar target inhibition in cells

Dietary Diversity Is Positively Associated with Deviation from Expected Height in Rural Nepal.

BACKGROUND: Recent research has highlighted the need for additional studies on the nutrition input required to stabilize growth. OBJECTIVE: Our objective was to examine the association between dietary diversity and conditional growth in children aged 0-89 mo. METHODS: We analyzed cohort data from 529 mothers and children living in a remote and food-insecure region in the mountains of Nepal. Children were aged 0-59 mo at baseline and were followed up after 9 and 29 mo. Conditional growth was calculated as the deviation from the expected height-for-age difference (HAD) trajectory based on previous measures of HAD and the pattern of growth in the population. Dietary diversity was assessed with the use of a count of the foods consumed from 7 food groups in the previous 7 d. The association between dietary diversity and conditional growth during the 2 follow-up periods (of 9 and 20 mo, respectively) was estimated with the use of ordinary least-squares regressions. RESULTS: Prevalence of stunting and absolute height deficits was very high and increased over the course of the study. At the last measurement (age range 29-89 mo), 76.5% were stunted and the mean ± SD HAD was -11.7 ± 4.6 cm. Dietary diversity was associated positively with conditional growth in the later (May 2012-December 2013) but not the earlier (July 2011-May 2012) growth period. Children's ages ranged from 0 to 59 mo in July 2011, 9 to 69 mo in May 2012, and 29 to 89 mo in December 2013. After adjustment, increasing the dietary diversity by one food group was associated with a 0.09 cm (95% CI: 0.00, 0.17 cm) increase in conditional growth in the second growth period. CONCLUSIONS: Increasing dietary diversity for children reduces the risk of stunting and improves growth after growth faltering. Future efforts should be directed at enabling families in food-insecure areas to feed their children a more diverse diet

Discovery of enzymes for toluene synthesis from anoxic microbial communities

Microbial toluene biosynthesis was reported in anoxic lake sediments more than three decades ago, but the enzyme catalyzing this biochemically challenging reaction has never been identified. Here we report the toluene-producing enzyme PhdB, a glycyl radical enzyme of bacterial origin that catalyzes phenylacetate decarboxylation, and its cognate activating enzyme PhdA, a radical S-adenosylmethionine enzyme, discovered in two distinct anoxic microbial communities that produce toluene. The unconventional process of enzyme discovery from a complex microbial community (>300,000 genes), rather than from a microbial isolate, involved metagenomics- and metaproteomics-enabled biochemistry, as well as in vitro confirmation of activity with recombinant enzymes. This work expands the known catalytic range of glycyl radical enzymes (only seven reaction types had been characterized previously) and aromatic-hydrocarbon-producing enzymes, and will enable first-time biochemical synthesis of an aromatic fuel hydrocarbon from renewable resources, such as lignocellulosic biomass, rather than from petroleum