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Colin Norman reports from Washington on US efforts to control the export trade in strategic technology being stimulated by the era of “détente”

Colin Norman in Washington examines the history and prospects of the Office of Technology Assessment

Colin Norman reports from Washington on US efforts to legislate on the controversial matter of toxic substances

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The 'war on cancer' has run off course. Efforts must refocus on the best interests of patients, says Colin Macilwain.

An oil slick will not re-engage the public with environmental issues, warns Colin Macilwain, but it might lead to a saner US energy policy.

Although there is plenty of shale oil in the United States, treatment at the surface of the rock that contains the oil would require prohibitive amounts of water. But the alternative, production in situ, is not yet a well developed technique.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

The United States government is planning to spend more than $10,000 million to develop a liquid metal fast breeder reactor. The programme is the highest priority energy research and development effort supported by public funds, but it has recently come under heavy criticism and it is beset by technical problems. In the second of a series of three articles, Colin Norman reports.

Colin Norman reports from Washington on President Carter's proposed budget changes

The nuclear exporters meet again soon. Colin Norman reports on the debate now taking place in the United States

Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.

The nuclear factor kappa B subunit c-Rel acts as a master regulator of metabolism and signalling in epithelial cells and macrophages that drives inflammation and fibrogenesis in various models of fibrosis.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The function of wild-type KRAS in KRAS mutant cancers remains to be explored. Here, the authors show that deletion of the tumour-suppressive wild-type Kras in a KRASG12D driven colon cancer model exacerbates tumour initiation in a MAPK dependent manner, while acting to suppress metastasis through impaired immune suppression.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.

Glutamine synthetase is the only enzyme that synthesizes glutamine in mammals. In vivo metabolomics showed that glutamine synthetase utilizes methylamine to produce N⁵-methylglutamine, whose levels correlate with tumor burden in a β+catenin+mutant liver cancer model.

It remains critical to identify colorectal cancers (CRC) that will disseminate as early as possible. Here, the authors identify CRC tumours that are aggressive and prone to early dissemination, characterised by epithelial TGFβ and growth-factor signalling - which could be targeted with MEK/EGFR inhibitors.

Tackling the loss of expensive cofactors is a key challenge in continuous-flow biocatalysis. This work reports immobilized enzymes with a tethered cofactor that is channelled between a recycling and a catalysis module facilitating total turnover numbers of NAD⁺ and ATP exceeding 10,000 in biocatalytic flow systems.

Glutamatergic neurons in the mammalian cortex are born from a heterogeneous pool of embryonic progenitors, however, it is unclear how these different progenitors contribute to diversity within the mature cortex. In this study, authors combine in utero progenitor labeling techniques with targeted Patch-Seq methods and high resolution synaptic circuit mapping in the mature mouse cortex to show that intermediate progenitors can generate restricted sets of transcriptomically-defined glutamatergic neurons that have distinct patterns of local and long-range synaptic connections.

In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.

NOTUM from Apc-mutant cells acts as a key mediator during the early stages of mutation fixation and drives the formation of intestinal adenomas.

Right-sided colorectal cancer (rCRC) has a different mutational spectrum to the left-sided counterpart. Here the authors develop a mouse model of rCRC that recapitulates human BRAF-mutant rCRC and show that loss of TGFβ-receptor signalling and inflammation induce the development of colonic tumours with a foetal-like phenotype.

Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

Colorectal tumors with mutated KRAS and APC require the amino acid transporter SLC7A5 to drive tumorigenesis. Mechanistically, SLC7A5 drives transcriptional and metabolic reprogramming by maintaining intracellular amino acid levels, leading to enhanced protein synthesis.

RAC1 is a downstream target of the Wnt signaling that promotes intestinal stem cell expansion and tumorigenesis. Here, the authors identify the specific splice variant RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment.

Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.

Glutamine metabolism is well known to support tumour growth. Here the authors show that cancer cells also utilize glutamine to promote invasiveness by converting it to glutamate, which upon secretion activates metabotropic glutamate receptors to stimulate matrix metalloproteases recycling to the cell surface.

SDH inactivation is associated with cancer susceptibility. Cardaci et al. report a metabolic vulnerability in SDH-deficient cells, by showing that they depend on pyruvate carboxylation for the production of aspartate, proliferation and tumour growth.

Mannose reduces the growth of tumour cells by impairing the metabolism of glucose, and enhances cell death when used in combination with conventional chemotherapy.

Platypuses are monotremes and combine aspects of both reptilian and mammalian behaviour. An international consortium reports the genome sequence and analysis of Ornithorhynchus anatinus and as expected, parts of the genome look more like mammals, whereas other parts more like reptiles or even chickens.