Summary
Tricin 5,7‐dihydroxy‐2‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐4H‐chromen‐4‐one, a flavone, was recently established as an authentic monomer in grass lignification that likely functions as a ...nucleation site. It is linked onto lignin as an aryl alkyl ether by radical coupling with monolignols or their acylated analogs. However, the level of tricin that incorporates into lignin remains unclear. Herein, three lignin characterization methods: acidolysis; thioacidolysis; and derivatization followed by reductive cleavage; were applied to quantitatively assess the amount of lignin‐integrated tricin. Their efficiencies at cleaving the tricin‐(4′–O–β)‐ether bonds and the degradation of tricin under the corresponding reaction conditions were evaluated. A hexadeuterated tricin analog was synthesized as an internal standard for accurate quantitation purposes. Thioacidolysis proved to be the most efficient method, liberating more than 91% of the tricin with little degradation. A survey of different seed‐plant species for the occurrence and content of tricin showed that it is widely distributed in the lignin from species in the family Poaceae (order Poales). Tricin occurs at low levels in some commelinid monocotyledon families outside the Poaceae, such as the Arecaceae (the palms, order Arecales) and Bromeliaceae (Poales), and the non‐commelinid monocotyledon family Orchidaceae (Orchidales). One eudicotyledon was found to have tricin (Medicago sativa, Fabaceae). The content of lignin‐integrated tricin is much higher than the extractable tricin level in all cases. Lignins, including waste lignin streams from biomass processing, could therefore provide a large and alternative source of this valuable flavone, reducing the costs, and encouraging studies into its application beyond its current roles.
Significance Statement
Tricin, a flavone with human health benefits, is covalently linked to lignin in monocots. Here we developed a chemical degradative method to quantify lignin‐integrated tricin. If methods to economically cleave tricin from lignin are developed, waste lignin streams from biomass processing could be used as an alternative source of tricin.
RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-κB activation, apoptosis, and necroptosis through its kinase and scaffolding activities. Dissecting the balance of RIP1 kinase activity and ...scaffolding function in vivo during development and TNF-dependent inflammation has been hampered by the perinatal lethality of RIP1-deficient mice. In this study, we generated RIP1 kinase-dead (Ripk1(K45A)) mice and showed they are viable and healthy, indicating that the kinase activity of RIP1, but not its scaffolding function, is dispensable for viability and homeostasis. After validating that the Ripk1(K45A) mice were specifically protected against necroptotic stimuli in vitro and in vivo, we crossed them with SHARPIN-deficient cpdm mice, which develop severe skin and multiorgan inflammation that has been hypothesized to be mediated by TNF-dependent apoptosis and/or necroptosis. Remarkably, crossing Ripk1(K45A) mice with the cpdm strain protected against all cpdm-related pathology. Together, these data suggest that RIP1 kinase represents an attractive therapeutic target for TNF-driven inflammatory diseases.
A synchrotron wide-angle x-ray scattering study of mung bean (Vigna radiata) primary cell walls was combined with published solid-state nuclear magnetic resonance data to test models for packing of ...(1→4)-β-glucan chains in cellulose microfibrils. Computer-simulated peak shapes, calculated for 36-chain microfibrils with perfect order or uncorrelated disorder, were sharper than those in the experimental diffractogram. Introducing correlated disorder into the models broaden the simulated peaks but only when the disorder was increased to unrealistic magnitudes. Computer-simulated diffractograms, calculated for 24- and 18-chain models, showed good fits to experimental data. Particularly good fits to both x-ray and nuclear magnetic resonance data were obtained for collections of 18-chain models with mixed cross-sectional shapes and occasional twinning. Synthesis of 18-chain microfibrils is consistent with a model for cellulose-synthesizing complexes in which three cellulose synthase polypeptides form a particle and six particles form a rosette.
Xylans with a variety of structures have been characterised in green algae, including chlorophytes (Chlorophyta) and charophytes (in the Streptophyta), and red algae (Rhodophyta). Substituted ...1,4-β-d-xylans, similar to those in land plants (embryophytes), occur in the cell wall matrix of advanced orders of charophyte green algae. Small proportions of 1,4-β-d-xylans have also been found in the cell walls of some chlorophyte green algae and red algae but have not been well characterised. 1,3-β-d-Xylans occur as triple helices in microfibrils in the cell walls of chlorophyte algae in the order Bryopsidales and of red algae in the order Bangiales. 1,3;1,4-β-d-Xylans occur in the cell wall matrix of red algae in the orders Palmariales and Nemaliales. In the angiosperm
, the gene
encodes a xylan 1,4-β-d-xylosyltranferase (xylan synthase), and, when heterologously expressed, this protein catalysed the production of the backbone of 1,4-β-d-xylans. An orthologous gene from the charophyte green alga
, when heterologously expressed, produced a similar protein that was also able to catalyse the production of the backbone of 1,4-β-d-xylans. Indeed, it is considered that land plant xylans evolved from xylans in ancestral charophyte green algae. However, nothing is known about the biosynthesis of the different xylans found in chlorophyte green algae and red algae. There is, thus, an urgent need to identify the genes and enzymes involved.
Studies of fully-reconstructed jets in heavy-ion collisions aim at extracting thermodynamical and transport properties of hot and dense QCD matter. Recently, a plethora of new jet substructure ...observables have been theoretically and experimentally developed that provide novel precise insights on the modifications of the parton radiation pattern induced by a QCD medium. This report, summarizing the main lines of discussion at the 5th Heavy Ion Jet Workshop and CERN TH institute 'Novel tools and observables for jet physics in heavy-ion collisions' in 2017, presents a first attempt at outlining a strategy for isolating and identifying the relevant physical processes that are responsible for the observed medium-induced jet modifications. These studies combine theory insights, based on the Lund parton splitting map, with sophisticated jet reconstruction techniques, including grooming and background subtraction algorithms.
Mesoscale convective systems (MCSs) produce some of the most intense rainfall on the planet, and their response to climate variability and change is rather uncertain. Under global warming, increased ...water vapor is expected to intensify the most extreme rain events and enhance flood frequency. However, MCS dynamics are also sensitive to other atmospheric variables, most notably, wind shear. Here we build on a recent study showing strong MCS intensification in the African Sahel, and examine evidence of similar trends elsewhere in tropical Africa. Using satellite data, we find a remarkable increase post‐1999 in intense MCS frequency over the Congo Basin during the month of February. This earlier onset of the spring rainy season has been accompanied by strong increases in the February meridional temperature gradient and associated wind shear. This supports the hypothesis that contrasts in warming across the continent can drive important decadal‐scale trends in storm intensity.
Plain Language Summary
Understanding how storms will change in a warming world is a major scientific challenge and one that has important impacts on society. Changes in the amount of atmospheric water vapor is considered to be the major driver for historical and future trends in intense storms. Here we examine how the intensity of storms over equatorial Africa has evolved since the early 1980s. Building on a previous landmark study over the semiarid Sahel region of North Africa, we identify that substantial storm intensification has taken place over the tropical forests of the Congo Basin, in February, marking the start of the first rainy season. The number of intense storms in that month has jumped by more than 100% since 1999, coinciding with a warming of 2 °C in the more arid parts of North‐Eastern Africa. Episodes of high temperatures over Sudan change the winds and moisture over the Congo Basin, and these factors favor more explosive storms. This provides additional evidence that African storms are sensitive to changes in temperature gradients across the continent and not just atmospheric humidity. These gradients are expected to increase with climate change, likely raising the frequency of flood events.
Key Points
Thirty‐five years of satellite data reveal an MCS intensification trend over equatorial Africa in February
There is a strong interannual correlation between Congo MCS intensity and temperature over the Eastern Sahel and Sahara
Upper‐level wave trains from the extratropics are implicated in Sahelian warm events
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The RAS–RAF–MEK–ERK, or ERK signaling pathway propagates signals through an intracellular signal transduction cascade. Since approximately one third of human cancers are impacted by ...mutations in the ERK signaling pathway, intensive efforts to develop drugs targeting members of this cascade are ongoing. While efforts to develop drugs aimed at inhibiting RAS are still at an early stage, substantial progress in discovering clinical drugs targeting RAF, MEK, and ERK have been made. This review will highlight the recent progress in this area.
Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial ...damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity.
Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 ...(RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCIIhiTNFα+IFNγ+ immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human PDA. Targeting RIP1 synergized with PD1-and inducible co-stimulator-based immunotherapies. Tumor-promoting effects of RIP1 were independent of its co-association with RIP3. Collectively, our work describes RIP1 as a checkpoint kinase governing tumor immunity.
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•RIP1 promotes tolerogenic macrophage differentiation via suppression of STAT1 in cancer•GSK′547 (RIP1i) is a mono-selective kinase inhibitor that robustly targets RIP1 in vivo•RIP1i is tumor-protective via macrophage-mediated Th1/Th17 and CTL activation•RIP1i synergizes with checkpoint- and co-stimulatory receptor-based immunotherapies
Wang et al. synthesize a selective RIP1 inhibitor that can be used in vivo. Inhibition of RIP1, which is highly expressed in tumor-associated macrophages in pancreatic ductal adenocarcinoma, reverses local immune suppression and enhances the efficacy of checkpoint- and co-stimulatory receptor-based immunotherapy.
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