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Storm Coley posted an update 6 months, 3 weeks ago
Forests have re-taken centre stage in global conversations about sustainability, climate and biodiversity. Here, we use a horizon scanning approach to identify five large-scale trends that are likely to have substantial medium- and long-term effects on forests and forest livelihoods forest megadisturbances; changing rural demographics; the rise of the middle-class in low- and middle-income countries; increased availability, access and use of digital technologies; and large-scale infrastructure development. These trends represent human and environmental processes that are exceptionally large in geographical extent and magnitude, and difficult to reverse. They are creating new agricultural and urban frontiers, changing existing rural landscapes and practices, opening spaces for novel conservation priorities and facilitating an unprecedented development of monitoring and evaluation platforms that can be used by local communities, civil society organizations, governments and international donors. Understanding these larger-scale dynamics is key to support not only the critical role of forests in meeting livelihood aspirations locally, but also a range of other sustainability challenges more globally. We argue that a better understanding of these trends and the identification of levers for change requires that the research community not only continue to build on case studies that have dominated research efforts so far, but place a greater emphasis on causality and causal mechanisms, and generate a deeper understanding of how local, national and international geographical scales interact.The insertion of magnesium into protoporphyrin initiates the biosynthesis of chlorophyll, the pigment that underpins photosynthesis. This reaction, catalysed by the magnesium chelatase complex, couples ATP hydrolysis by a ChlID motor complex to chelation within the ChlH subunit. We probed the structure and catalytic function of ChlH using a combination of X-ray crystallography, computational modelling, mutagenesis and enzymology. Two linked domains of ChlH in an initially open conformation of ChlH bind protoporphyrin IX, and the rearrangement of several loops envelops this substrate, forming an active site cavity. This induced fit brings an essential glutamate (E660), proposed to be the key catalytic residue for magnesium insertion, into proximity with the porphyrin. A buried solvent channel adjacent to E660 connects the exterior bulk solvent to the active site, forming a possible conduit for the delivery of magnesium or abstraction of protons.Innovative approaches are urgently required to alleviate the growing pressure on agriculture to meet the rising demand for food. A key challenge for plant biology is to bridge the notable knowledge gap between our detailed understanding of model plants grown under laboratory conditions and the agriculturally important crops cultivated in fields or production facilities. This Perspective highlights the recent development of new analytical tools that are rapid and non-destructive and provide tissue-, cell- or organelle-specific information on living plants in real time, with the potential to extend across multiple species in field applications. We evaluate the utility of engineered plant nanosensors and portable Raman spectroscopy to detect biotic and abiotic stresses, monitor plant hormonal signalling as well as characterize the soil, phytobiome and crop health in a non- or minimally invasive manner. We propose leveraging these tools to bridge the aforementioned fundamental gap with new synthesis and integration of expertise from plant biology, engineering and data science. Lastly, we assess the economic potential and discuss implementation strategies that will ensure the acceptance and successful integration of these modern tools in future farming practices in traditional as well as urban agriculture.In non-small-cell lung cancer (NSCLC), concurrent mutations in the oncogene KRAS and the tumour suppressor STK11 (also known as LKB1) encoding the kinase LKB1 result in aggressive tumours prone to metastasis but with liabilities arising from reprogrammed metabolism. We previously demonstrated perturbed nitrogen metabolism and addiction to an unconventional pathway of pyrimidine synthesis in KRAS/LKB1 co-mutant cancer cells. To gain broader insight into metabolic reprogramming in NSCLC, we analysed tumour metabolomes in a series of genetically engineered mouse models with oncogenic KRAS combined with mutations in LKB1 or p53. Metabolomics and gene expression profiling pointed towards activation of the hexosamine biosynthesis pathway (HBP), another nitrogen-related metabolic pathway, in both mouse and human KRAS/LKB1 co-mutant tumours. KRAS/LKB1 co-mutant cells contain high levels of HBP metabolites, higher flux through the HBP pathway and elevated dependence on the HBP enzyme glutamine-fructose-6-phosphate transaminase 2 (GFPT2). GFPT2 inhibition selectively reduced KRAS/LKB1 co-mutant tumour cell growth in culture, xenografts and genetically modified mice. learn more Our results define a new metabolic vulnerability in KRAS/LKB1 co-mutant tumours and provide a rationale for targeting GFPT2 in this aggressive NSCLC subtype.The in vitro differentiation of insulin-producing beta-like cells can model aspects of human pancreatic development. Here, we generate 95,308 single-cell transcriptomes and reconstruct a lineage tree of the entire differentiation process from human embryonic stem cells to beta-like cells to study temporally regulated genes during differentiation. We identify so-called ‘switch genes’ at the branch point of endocrine/non-endocrine cell fate choice, revealing insights into the mechanisms of differentiation-promoting reagents, such as NOTCH and ROCKII inhibitors, and providing improved differentiation protocols. Over 20% of all detectable genes are activated multiple times during differentiation, even though their enhancer activation is usually unimodal, indicating extensive gene reuse driven by different enhancers. We also identify a stage-specific enhancer at the TCF7L2 locus for diabetes, uncovered by genome-wide association studies, that drives a transient wave of gene expression in pancreatic progenitors. Finally, we develop a web app to visualize gene expression on the lineage tree, providing a comprehensive single-cell data resource for researchers studying islet biology and diabetes.
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