Hyperactive gp130/STAT3-driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development

Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation-associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour-associated TLSs remain ill-defined. Here, we observed tumour-associated TLSs in a preclinical mouse model (gp130F/F) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL-6 family signalling receptor, gp130. Gastric tumourigenesis was associated with the development of B and T cell-rich submucosal lymphoid aggregates, containing CD21+ cellular networks and high endothelial venules. Temporally, TLS formation coincided with the development of gastric adenomas and induction of homeostatic chemokines including Cxcl13, Ccl19 and Ccl21. Reflecting the requirement of gp130-driven STAT3 signalling for gastric tumourigenesis, submucosal TLS development was also STAT3-dependent, but independent of the cytokine IL-17 which has been linked with lymphoid neogenesis in chronic inflammation and autoimmunity. Interestingly, upregulated lymphoid chemokine expression and TLS formation were also observed in a chronic gastritis model induced by Helicobacter felis infection. Tumour-associated TLSs were also observed in patients with intestinal-type gastric cancer, and a gene signature linked with TLS development in gp130F/F mice was associated with advanced clinical disease, but was not prognostic of patient survival. Collectively, our in vivo data reveal that hyperactive gp130-STAT3 signalling closely links gastric tumourigenesis with lymphoid neogenesis, and while a TLS gene signature was associated with advanced gastric cancer in patients, it did not indicate a favourable prognosis

Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment

Model comparisons for estimating carbon emissions from North American wildland fire

Research activities focused on estimating the direct emissions of carbon from wildland fires across North America are reviewed as part of the North American Carbon Program disturbance synthesis. A comparison of methods to estimate the loss of carbon from the terrestrial biosphere to the atmosphere from wildland fires is presented. Published studies on emissions from recent and historic time periods and five specific cases are summarized, and new emissions estimates are made using contemporary methods for a set of specific fire events. Results from as many as six terrestrial models are compared. We find that methods generally produce similar results within each case, but estimates vary based on site location, vegetation (fuel) type, and fire weather. Area normalized emissions range from 0.23 kg C m−2 for shrubland sites in southern California/NW Mexico to as high as 6.0 kg C m−2 in northern conifer forests. Total emissions range from 0.23 to 1.6 Tg C for a set of 2003 fires in chaparral-dominated landscapes of California to 3.9 to 6.2 Tg C in the dense conifer forests of western Oregon. While the results from models do not always agree, variations can be attributed to differences in model assumptions and methods, including the treatment of canopy consumption and methods to account for changes in fuel moisture, one of the main drivers of variability in fire emissions. From our review and synthesis, we identify key uncertainties and areas of improvement for understanding the magnitude and spatial-temporal patterns of pyrogenic carbon emissions across North America

Initial experience with an electron FLASH research extension (FLEX) for the Clinac system

Purpose: Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. Methods: A linear accelerator (Clinac 23EX) was modified to include a nonclinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. Results: The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached amaximum dose rate \u3e3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes \u3e10 × 10 cm2. The output stability of the FLASH system exhibited a dose deviation of \u3c1%.Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. Conclusion: Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists

Oyster reef restoration - aquaculture interactions: maximizing positive synergies

Globally, oyster reef restoration is on the rise. In many instances, restoration is occurring alongside established oyster aquaculture industries that grew to prominence following oyster reef demise. This paper examines the potential positive and negative interactions between the two industries and identifies key factors that may promote positive interactions. Interactions between the two industries result from shared resource requirements (e.g., space, clean water, brood-stock, breeding programs), shared knowledge requirements (e.g. around threats and their mitigation, factors optimizing growth/survival) and biological interactions (e.g. over-catch, disease spill-over, competition for resources). Many of these interactions are reciprocated, and can shift from positive to negative depending on environmental, biological and socio-economic conditions. From our examination, three key factors emerge as shaping the strength and direction (positive or negative) of interactions: (1) whether the focal species is common or different between the two industries; (2) the physicochemical and socio-economic environment in which the two industries are occurring; and (3) whether there is open dialogue and consultation between the two industries and relevant stakeholders. Positive interactions can be maximized where the two industries are able to co-invest in and share infrastructure (e.g. hatcheries, breeding programs), resources (e.g. spat, broodstock, shell) and knowledge (e.g. optimal conditions of growth) – an easier task where the target oyster species is in common. Positive interactions may also be maximized by utilizing marine spatial planning tools, such as suitability modelling, to inform optimal siting of the two industries. As the two industries continue to grow, open and inclusive dialogue between these and key stakeholders will be essential for mitigating risk and maximising positive synergies

Burned area and carbon emissions across northwestern boreal North America from 2001-2019

Fire is the dominant disturbance agent in Alaskan and Canadian boreal ecosystems and releases large amounts of carbon into the atmosphere. Burned area and carbon emissions have been increasing with climate change, which have the potential to alter the carbon balance and shift the region from a historic sink to a source. It is therefore critically important to track the spatiotemporal changes in burned area and fire carbon emissions over time. Here we developed a new burned-area detection algorithm between 2001-2019 across Alaska and Canada at 500 m (meters) resolution that utilizes finer-scale 30 m Landsat imagery to account for land cover unsuitable for burning. This method strictly balances omission and commission errors at 500 m to derive accurate landscape- and regional-scale burned-area estimates. Using this new burned-area product, we developed statistical models to predict burn depth and carbon combustion for the same period within the NASA Arctic-Boreal Vulnerability Experiment (ABoVE) core and extended domain. Statistical models were constrained using a database of field observations across the domain and were related to a variety of response variables including remotely sensed indicators of fire severity, fire weather indices, local climate, soils, and topographic indicators. The burn depth and aboveground combustion models performed best, with poorer performance for belowground combustion. We estimate 2.37×106 ha (2.37 Mha) burned annually between 2001-2019 over the ABoVE domain (2.87 Mha across all of Alaska and Canada), emitting 79.3 ± 27.96 Tg (±1 standard deviation) of carbon (C) per year, with a mean combustion rate of 3.13 ± 1.17 kg C m-2. Mean combustion and burn depth displayed a general gradient of higher severity in the northwestern portion of the domain to lower severity in the south and east. We also found larger-fire years and later-season burning were generally associated with greater mean combustion. Our estimates are generally consistent with previous efforts to quantify burned area, fire carbon emissions, and their drivers in regions within boreal North America; however, we generally estimate higher burned area and carbon emissions due to our use of Landsat imagery, greater availability of field observations, and improvements in modeling. The burned area and combustion datasets described here (the ABoVE Fire Emissions Database, or ABoVE-FED) can be used for local- to continental-scale applications of boreal fire science

A dense mini-Neptune orbiting the bright young star HD 18599

© 2022 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stac2845Very little is known about the young planet population because the detection of small planets orbiting young stars is obscured by the effects of stellar activity and fast rotation which mask planets within radial velocity and transit data sets. The few planets that have been discovered in young clusters generally orbit stars too faint for any detailed follow-up analysis. Here we present the characterization of a new mini-Neptune planet orbiting the bright (V=9) and nearby K2 dwarf star, HD 18599. The planet candidate was originally detected in TESS light curves from Sectors 2, 3, 29, and 30, with an orbital period of 4.138~days. We then used HARPS and FEROS radial velocities, to find the companion mass to be 25.5$\pm$4.6~M$_\oplus$. When we combine this with the measured radius from TESS, of 2.70$\pm$0.05~R$_\oplus$, we find a high planetary density of 7.1$\pm$1.4~g cm$^{-3}$. The planet exists on the edge of the Neptune Desert and is the first young planet (300 Myr) of its type to inhabit this region. Structure models argue for a bulk composition to consist of 23% H$_2$O and 77% Rock and Iron. Future follow-up with large ground- and space-based telescopes can enable us to begin to understand in detail the characteristics of young Neptunes in the galaxy.Peer reviewe

Temporal and spectral multiplexing for EUV multibeam ptychography with a high harmonic light source

We demonstrate temporally multiplexed multibeam ptychography implemented for the first time in the EUV, by using a high harmonic based light source. This allows for simultaneous imaging of different sample areas, or of the same area at different times or incidence angles. Furthermore, we show that this technique is compatible with wavelength multiplexing for multibeam spectroscopic imaging, taking full advantage of the temporal and spectral characteristics of high harmonic light sources. This technique enables increased data throughput using a simple experimental implementation and with high photon efficiency. &nbsp;</p

Th1 cells alter the inflammatory signature of IL-6 by channeling STAT transcription factors to Alu-like retroelements

Cytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, anti-microbial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA-seq, ChIP-seq, and ATAC-seq to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues during acute resolving inflammation and inflammation primed to drive fibrosis. Bioinformatics focussed on the transcriptional signature of the immuno-modulatory cytokine IL-6 in both settings and examined how pro-fibrotic IFNg- secreting CD4+ T-cells altered the interpretation of STAT1 and STAT3 cytokine cues. In resolving inflammation, STAT1 and STAT3 cooperated to drive stromal gene expression affecting anti-microbial immunity and tissue homeostasis. The introduction of IFNg-secreting CD4+ T-cells altered this transcriptional program and channeled STAT1 and STAT3 to a previously latent GAS motif in Alu-like elements. STAT1 and STAT3 binding to this conserved sequence revealed evidence of reciprocal cross-regulation and gene signatures relevant to pathophysiology. Thus, we propose that effector T-cells re-tune the transcriptional output of IL-6 by shaping a regulatory interplay between STAT1 and STAT3 in inflammation

Two mini-Neptunes Transiting the Adolescent K-star HIP 113103 Confirmed with TESS and CHEOPS

We report the discovery of two mini-Neptunes in near 2:1 resonance orbits ($P=7.610303$ d for HIP 113103 b and $P=14.245651$ d for HIP 113103 c) around the adolescent K-star HIP 113103 (TIC 121490076). The planet system was first identified from the TESS mission, and was confirmed via additional photometric and spectroscopic observations, including a $\sim$17.5 hour observation for the transits of both planets using ESA CHEOPS. We place $\leq4.5$ min and $\leq2.5$ min limits on the absence of transit timing variations over the three year photometric baseline, allowing further constraints on the orbital eccentricities of the system beyond that available from the photometric transit duration alone. With a planetary radius of $R_{p}=1.829^{+0.096}_{-0.067}\,R_{\oplus}$, HIP 113103 b resides within the radius gap, and this might provide invaluable information on the formation disparities between super-Earths and mini-Neptunes. Given the larger radius $R_{p}=2.40^{+0.10}_{-0.08}\,R_{\oplus}$ for HIP 113103 c, and close proximity of both planets to HIP 113103, it is likely that HIP 113103 b might have lost (or is still losing) its primordial atmosphere. We therefore present simulated atmospheric transmission spectra of both planets using JWST, HST, and Twinkle. It demonstrates a potential metallicity difference (due to differences in their evolution) would be a challenge to detect if the atmospheres are in chemical equilibrium. As one of the brightest multi sub-Neptune planet systems suitable for atmosphere follow up, HIP 113103 b and HIP 113103 c could provide insight on planetary evolution for the sub-Neptune K-star population.Comment: 18 pages, 12 figures, accepted for publication in the Monthly Notices of the Royal Astronomical Societ