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DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used tow...
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DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used toward the development of therapeutics for cancers and viral treatments. We used the WDR domain of DCAF1 to screen a 114-billion-compound DNA encoded library (DEL) and identified candidate compounds using similarity search and machine learning. This led to the discovery of a compound (Z1391232269) with an SPR KD of 11 mu M. Structure-guided hit optimization led to the discovery of OICR-8268 (26e) with an SPR KD of 38 nM and cellular target engagement with EC50 of 10 mu M as measured by cellular thermal shift assay (CETSA). OICR-8268 is an excellent tool compound to enable the development of next-generation DCAF1 ligands toward cancer therapeutics, further investigation of DCAF1 functions in cells, and the development of DCAF1-based PROTACs.
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USP5 is a deubiquitinase that has been implicated in a range of diseases, including cancer, but no USP5-targeting chemical probe has been reported to date. Here, we present the progression of a chemical series that occupies the C-...
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USP5 is a deubiquitinase that has been implicated in a range of diseases, including cancer, but no USP5-targeting chemical probe has been reported to date. Here, we present the progression of a chemical series that occupies the C-terminal ubiquitin-binding site of a poorly characterized zinc-finger ubiquitin binding domain (ZnF-UBD) of USP5 and competitively inhibits the catalytic activity of the enzyme. Exploration of the structure-activity relationship, complemented with crystallo-graphic characterization of the ZnF-UBD bound to multiple ligands, led to the identification of 64, which binds to the USP5 ZnF-UBD with a K-D of 2.8 mu M and is selective over nine proteins containing structurally similar ZnF-UBD domains. 64 inhibits the USP5 catalytic cleavage of a di-ubiquitin substrate in an in vitro assay. This study provides a chemical and structural framework for the discovery of a chemical probe to delineate USP5 function in cells.
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Previous research on increasing soil carbon sequestration, through soil carbon management (SCM), has not integrated social components into the ecological system. To understand how experienced farmers combine social and ecological ...
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Previous research on increasing soil carbon sequestration, through soil carbon management (SCM), has not integrated social components into the ecological system. To understand how experienced farmers combine social and ecological components of soil carbon management practices, we have used a social-ecological systems (SES) framework. This study examines the distribution and pattern of farmers' SCM practices, comparing and contrasting two farming cohorts based on inherent soil fertility in a rotational grazing regime of sub-tropical temperate grazing lands in Australia. Twenty-five grazing farmers with the land of low (n= 13) and moderate (n=12) fertility soils were interviewed about SCM and how they have maintained their grazing regime despite climatic constraints using the SES framework. Both farming cohorts (low-fertility farms and moderate-fertility farms) have shown resolve to continue their grazing regime because the benefits were manifold and affected the whole-farm sustainability. Farmers with low-fertility farms highlighted a number of SCM outcomes but were less confident of achieving them. Farmers were focused on the agri-environmental benefits of SCM practices in a holistic manner, rather than a single goal of increasing soil carbon. The interviewed farmers reported a number of benefits that accrue from their grazing regimes, including improvements in production, soil moisture retention, and soil health, even though some of these benefits were not measured. Farmers in more "stressed " environments, with low soil fertility, also emphasized mental health and landscape esthetics as outcomes of SCM. These features of the farmers' SCM provide important benefits that are not easily quantified but are also instrumental in encouraging other farmers to manage their soil. Long-term practitioners of rotational grazing such as the farmers in this study can provide useful insights for a more targeted, customized, and nuanced government policy that focuses on whole-farm sustainability, which can also improve soil carbon stocks in similar regions of Australia.
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This article reviews the current research and applications of various digital soil mapping (DSM) techniques used to map Soil Organic Carbon (SOC) concentration and stocks following a systematic mapping approach from 2013 until pre...
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This article reviews the current research and applications of various digital soil mapping (DSM) techniques used to map Soil Organic Carbon (SOC) concentration and stocks following a systematic mapping approach from 2013 until present (18 February 2019). It is intended that this review of relevant literature will assist prospective researchers by identifying knowledge clusters and gaps in relation to the digital mapping of SOC. Of 120 studies, most were clustered in some specific countries such as China, Australia and the USA. The highest number publications were in 2016 and 2017. Regarding the predictive models, there was a progression from Linear Models towards Machine Learning (ML) techniques, and hybrid models in Regression Kriging (RK) framework performed better than individual models. Multiple Linear Regression (MLR) was the most frequently used method for predicting SOC, although it was outperformed by other ML techniques in most studies. Random Forest (RF) was found to perform better than MLR and other ML techniques in most comparative studies. Other common and competitive techniques were Cubist, Neural Network (NN), Boosted Regression Tree (BRT), Support Vector Machine (SVM) and Geographically Weighted Regression (GWR). Due to the inconsistency in various comparative studies, it would be advisable to calibrate the competitive algorithms using specific experimental datasets. This review also reveals the environmental covariates that have been identified as the most important by RF technique in recent years in regard to digital mapping of SOC, which may assist in selecting optimum sets of environmental covariates for mapping SOC. Covariates representing organism/organic activities were among the most frequent among top five covariates, followed by the variables representing climate and topography. Climate was reported to be influential in determining the variation in SOC level at regional scales, followed by parent materials, topography and land use. However, for mapping at a resolution that represents smaller areas such as a farm- or plot-scale, land use and vegetation indices were stated to be more influential in predicting SOC. Furthermore, unlike a previous review work, all recent studies in this review incorporated validation and 41% of them estimated spatially explicit prediction of uncertainty. Only 9.16% studies performed external validation, whereas most studies used data-splitting and cross-validation techniques which may not be the best options for datasets obtained through non-probability sampling.
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Drivers of soil organic carbon (SOC) storage are likely to vary in importance in different regions and at different depths due to local factors influencing SOC dynamics. This paper explores the factors influencing SOC to a depth o...
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Drivers of soil organic carbon (SOC) storage are likely to vary in importance in different regions and at different depths due to local factors influencing SOC dynamics. This paper explores the factors influencing SOC to a depth of 30 cm in eastern Australia.
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Many people living in poverty ride bicycles and many also participate in informal work such as recycling. A small number of studies have begun to explore homeless cyclists' experiences with and perspectives on bicycles and recycli...
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Many people living in poverty ride bicycles and many also participate in informal work such as recycling. A small number of studies have begun to explore homeless cyclists' experiences with and perspectives on bicycles and recycling. In the current study, we seek to contribute to this emerging area of study, focusing in this case on the social support and informal and formal resources homeless and variably-housed cyclists use in Vancouver. Interviews, including go-along mobile methods, were conducted with five men living in the Downtown Eastside neighbourhood of Vancouver who use bicycles. Findings show that the cyclists, especially recyclers, navigated an 'underground economy' of bike-related spaces that allowed them to make money, keep their bicycles in working condition, and cultivate social connections. In particular, a few highly valuable sources and spaces of support existed for participants within a landscape where barriers of many sorts were encountered regularly. These findings bring attention to the needs of and resources considered to be most valuable for some cyclists living in poverty, to the creativity and resilience of an often stigmatised group, and to ways that more inclusive cycling policy might support the efforts of a marginalised group to live a healthy life.
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Plant roots are primary factors to contribute to surface and deep soil carbon sequestration (SCS). Perennial grasses like vetiver produce large and deep root system and are likely to contribute significantly to soil carbon. Howeve...
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Plant roots are primary factors to contribute to surface and deep soil carbon sequestration (SCS). Perennial grasses like vetiver produce large and deep root system and are likely to contribute significantly to soil carbon. However, we have limited knowledge on how root and shoot decomposition differ and their contribution to SCS. This study examined biomass production and relative decomposition of vetiver which was grown under glasshouse conditions. Subsequently the biomass incubated for 206 days, and the gas analysed using ANCA-GSL. The results confirmed large shoot and root production potential of 161 and 107 Mg ha?1 (fresh) and 67.7 and 52.5 Mg ha?1 (dry) biomass, respectively with 11.43 (fresh) and 11.25 (dry) production ratio. Vetiver roots decomposed more rapidly in the clay soil (p < 0.001) compared with the shoots, which could be attributed to the lower CN ratio of roots than the shoots. The large root biomass produced does indeed contribute more to the soil carbon accumulation and the faster root decomposition is crucial in releasing the carbon in the root exudates and would also speed up its contribution to stable SOM. Hence, planting vetiver and similar tropical perennial grasses on degraded and less fertile soils could be a good strategy to rehabilitate degraded soils and for SCS.
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In a rotation, the use of crop species with large root biomass is thought to increase soil organic carbon (SOC) storage deeper in the soil profile, yet the processes and mechanisms that control SOC dynamics at depth are poorly und...
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In a rotation, the use of crop species with large root biomass is thought to increase soil organic carbon (SOC) storage deeper in the soil profile, yet the processes and mechanisms that control SOC dynamics at depth are poorly understood. Using a cotton-based field trial, we examined how maize may impact SOC dynamics up to 1 m depth in three systems that differed in tillage and wheat rotation by examining the changes in delta C-13 signature of SOC and soil C fractions associated with maize during a two-year period. The inclusion of maize increased the whole-profile SOC stock, particularly in the subsoil under minimum tillage and wheat rotation. The increase was associated with the stable C fraction, and could not be attributed solely to the C contribution from maize root biomass alone. We propose that C movement in the form of dissolved organic C (DOC) may have contributed to the observed increase in SOC stock. The strong temporal changes and the possible mechanisms behind the increase suggest that the introduction of maize into cotton-based cropping systems may not yield a consistent benefit. This study highlights the role of DOC in subsoil C stock and the importance of understanding whole-profile SOC dynamics in evaluating the potential of management practice in increasing SOC stock.
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We investigated the stability of whole profile soil organic carbon (SOC) based upon three mid-infrared predicted fractions - particulate organic carbon (POC), humus organic carbon (HOC) and resistant organic carbon (ROC) - at 100 ...
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We investigated the stability of whole profile soil organic carbon (SOC) based upon three mid-infrared predicted fractions - particulate organic carbon (POC), humus organic carbon (HOC) and resistant organic carbon (ROC) - at 100 sites across eastern Australia. Our aim was to identify the controls on SOC stability down the whole soil profile, in particular relating to climate, site and human influences. To do this we used three data-mining algorithms (randomForests, gradient boosting machines and multiplicative adaptive regression splines) to identify and assess the controls on the relative proportions of the three fractions down the soil profile. Depth was the key influence on all three fractions, with the proportion of POC decreasing, and the proportion of HOC carbon increasing with increasing depth. SOC was strongly linked with POC, suggesting that the soils in the region are input driven. HOC and ROC were controlled additionally by climate and soil physico-chemical properties (e.g. clay content, pH), with SOC being less important to these fractions. Human influences (land-use and management) were not important to the proportion of the fractions, implying that the controls humans can exert on SOC stability in these environments may be limited. (C) 2016 Elsevier B.V. All rights reserved.
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The global shift or movement of commodities and products has been increasing through international trade recently. Although lead is a widely used material and easy to recycle, hence its high rate of recyclability, it is important ...
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The global shift or movement of commodities and products has been increasing through international trade recently. Although lead is a widely used material and easy to recycle, hence its high rate of recyclability, it is important to manage it in an environmentally sound manner due to its high toxicity. Lead is present in various lead bearing commodities and lead-containing products. One of the commodities is refined lead. Its principal use is in the production of lead acid electric accumulators (LAA), commonly known as lead acid batteries (LAB), for the automotive and industrial sectors. Two principal sources of refined lead production are: lead ores and concentrates, and used lead acid electric batteries (ULAB). During the period 1992-2012, it was observed that trade in both sources increased rapidly. The physical trade data for lead commodities and products have been collated and analyzed based on the Physical Trade Balance (PTB) in order to identify global suppliers and consumers of lead ores and concentrates, and LAB, as well as the information related to production and apparent consumption. 20 countries were identified whose movement of lead commodities and products accounted for at least 70% of the global physical trade and for the production and apparent consumption. The movement of lead ores and concentrates was limited to a few countries, however the LABs was diversified between 1992 and 2012. The concentrations of the lead commodities and products are located in China, the USA, Germany and Australia as major consumers and suppliers. The potential environmental and population health threats due to the lead industry were principally located in countries belonging to the emerging and developing economies or those in transition. (C) 2015 Elsevier Ltd. All rights reserved.
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