The effects of marine heatwaves on acute heat tolerance in corals

Scleractinian coral populations are increasingly exposed to conditions above their upper thermal limits due to marine heatwaves, contributing to global declines of coral reef ecosystem health. However, historic mass bleaching events indicate there is considerable inter- and intra-specific variation in thermal tolerance whereby species, individual coral colonies and populations show differential susceptibility to exposure to elevated temperatures. Despite this, we lack a clear understanding of how heat tolerance varies across large contemporary and historical environmental gradients, or the selective pressures that underpin this variation. Here we conducted standardised acute heat stress experiments to identify variation in heat tolerance among species and isolated reefs spanning a large environmental gradient across the Coral Sea Marine Park. We quantified the photochemical yield (F-v/F-m) of coral samples in three coral species, Acropora cf humilis, Pocillopora meandrina, and Pocillopora verrucosa, following exposure to four temperature treatments (local ambient temperatures, and + 3 degrees C, +6 degrees C and + 9 degrees C above local maximum monthly mean). We quantified the temperature at which F-v/F-m decreased by 50% (termed ED50) and used derived values to directly compare acute heat tolerance across reefs and species. The ED50 for Acropora was 0.4-0.7 degrees C lower than either Pocillopora species, with a 0.3 degrees C difference between the two Pocillopora species. We also recorded 0.9 degrees C to 1.9 degrees C phenotypic variation in heat tolerance among reefs within species, indicating spatial heterogeneity in heat tolerance across broad environmental gradients. Acute heat tolerance had a strong positive relationship to mild heatwave exposure over the past 35 years (since 1986) but was negatively related to recent severe heatwaves (2016-2020). Phenotypic variation associated with mild thermal history in local environments provides supportive evidence that marine heatwaves are selecting for tolerant individuals and populations; however, this adaptive potential may be compromised by the exposure to recent severe heatwaves

miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan.

INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0. Mutation status of KRAS, BRAF, and PI3KCA was known. RESULTS: After Bonferroni adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR-324-3p), were found associated with short OS. miR-345 was the strongest prognostic miRNA, significant in the full cohort and in the non-KRAS mutant population. miR-345, as a continuous variable in the full cohort, resulted in a hazard ratio (HR) of 2.38 per IQR (CI 95%: 1.8-3.1, P-value = 2.86e-07, Bonferroni adjusted, univariable analysis) and a HR = 1.75 per IQR (CI 95%: 1.24-2.48, P-Wald = 1.45e-03) in the multivariable analysis adjusted for gender, age, KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free survival (PFS) with a HR = 1.63 per IQR (CI 95%: 1.25-2.114, P-Wald = 2.92e-4) in the multivariable analysis. In addition, high miR-345 expression was associated with lack of response to treatment with cetuximab and irinotecan. CONCLUSION: We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population

Low bone turnover associates with lower insulin sensitivity in newly diagnosed drug-naïve persons with type 2 diabetes

Context Bone turnover markers (BTMs) are lower in type 2 diabetes mellitus (T2D). The relationships between bone turnover, β-cell function, and insulin sensitivity in T2D are uncertain. Objective To investigate if fasting levels of BTMs in persons with T2D are associated with β-cell function or insulin sensitivity. Methods We defined three T2D phenotypes, the insulinopenic (low β-cell function, high insulin sensitivity), the classical (low β-cell function, low insulin sensitivity), and the hyperinsulinemic (high β-cell function, low insulin sensitivity) phenotypes, in the Danish Centre for Strategic Research T2D cohort using the homeostatic model assessment. We selected age- and gender-matched subgroups to represent the three T2D phenotypes, yielding 326 glucose-lowering treatment–naïve persons with T2D. Median values of BTMs between the three T2D phenotypes were compared. Regression models were applied to assess the association between BTMs, β-cell function, and insulin sensitivity adjusted for potential confounders. Results Median serum levels of procollagen type I N-terminal propeptide, C-terminal telopeptide of type I collagen, and osteocalcin were higher in the insulinopenic phenotype (52.3 μg/L, IQR 41.6, 63.3; 259.4 ng/L, IQR 163.4, 347.7; and 18.0 μg/L, IQR 14.4, 25.2, respectively) compared with the classical (41.4, IQR 31.0, 51.4; 150.4 IQR 103.5, 265.1; 13.1, IQR 10.0, 17.6, respectively) and the hyperinsulinemic (43.7, IQR 32.3, 57.3; 163.3, IQR 98.9, 273.1; 15.7 IQR 10.2, 20.8, respectively) phenotypes (all P < .01). These differences persisted after adjustment for age, sex, waist to hip ratio, or fasting plasma glucose (P < .01). Conclusion BTMs are lower in newly diagnosed persons with T2D characterized by low insulin sensitivity

Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial

Aims Thiazolidinediones are insulin sensitizers, and are associated with fluid retention and increased risk of heart failure (HF) in people with type 2 diabetes. We assessed fatal and non-fatal HF events and their outcome, and identified HF predictors in the RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes) trial population. Methods and results In a multicentre, open-label study, we randomized 4447 people with type 2 diabetes on metformin or sulfonylurea monotherapy with a mean HbA(1c) of 7.9% to add-on rosiglitazone (n = 2220) or to a combination of metformin and sulfonylurea (n = 2227) and followed them over 5.5 years on average. Heart failure hospitalizations and deaths were adjudicated by a Clinical Endpoint Committee using pre-specified criteria. Independent predictors of HF events were identified out of a group of 30 pre-specified clinical, demographic, and biological variables. In the rosiglitazone group, the risk of HF death or hospitalization was doubled: HR = 2.10 (95% CI, 1.35-3.27): the excess HF event rate was 2.6 (1.1-4.1) per 1000 person-years. An excess in HF deaths was observed (10 vs. two), including four HF deaths as first HF events. By contrast, there was no increase in cardiovascular mortality or hospitalization (HR = 0.99, 95% Cl, 0.85-1.16) or in cardiovascular deaths (60 vs. 71). Independent predictors of HF were rosiglitazone assignment, age, urinary albumin : creatinine ratio, body mass index, and systolic blood pressure at baseline. A history of previous cardiovascular disease was not predictive of HF. Duration of HF hospitalization and rate of HF re-hospitalization were similar in the two groups. Conclusion These findings confirm the increased risk of HF events in people treated with rosiglitazone and support the recommendation that this agent should not continue to be used in people developing symptomatic HF while using the medication. Close follow-up for the risk of HF should be offered to elderly people, people with markedly increased body mass index, people with microalbuminuria/proteinuria, and people with increased systolic blood pressur

Transmission spectroscopy of the ultra-hot Jupiter MASCARA-4 b: disentangling the hydrostatic and exospheric regimes of ultra-hot Jupiters

Stars and planetary system

Background rejection in NEXT using deep neural networks

[EN] We investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed better than previous methods developed based on the use of the same topological signatures by a factor of 1.2 to 1.6, and there is potential for further improvement.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain and FEDER under grants CONSOLIDER-Ingenio 2010 CSD2008-0037 (CUP), FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398; GVA under grant PROMETEO/2016/120. Fermilab is operated by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the United States Department of Energy. JR acknowledges support from a Fulbright Junior Research Award.Renner, J.; Farbin, A.; Muñoz Vidal, J.; Benlloch-Rodríguez, J.; Botas, A.; Ferrario, P.; Gómez-Cadenas, J.... (2017). Background rejection in NEXT using deep neural networks. Journal of Instrumentation. 12. https://doi.org/10.1088/1748-0221/12/01/T01004S1

Two Intermediate-mass Transiting Brown Dwarfs from the TESS Mission

We report the discovery of two intermediate-mass transiting brown dwarfs (BDs), TOI-569b and TOI-1406b, from NASA's Transiting Exoplanet Survey Satellite mission. TOI-569b has an orbital period of P=.55604±0.00016 days, a mass of Mb = 64.1±1.9 MJ, and a radius of Rb = 0.75±0.02 RJ. Its host star, TOI-569, has a mass of Må = 1.21±0.05 M, a radius of Rå = 1.47±0.03 R, [Fe H 0.29 0.09] = + dex, and an effective temperature of Teff = 5768±10K. TOI-1406b has an orbital period of P=10.57415±0.00063 days, a mass of Mb = 46.0± 2.7 MJ, and a radius of Rb = 0.86±0.03 RJ. The host star for this BD has a mass of Må = 1.18±0.09 M, a radius of Rå = 1.35±0.03 R, [Fe/H] =-0.08± 0.09 dex, and an effective temperature of Teff = 6290±100 K. Both BDs are in circular orbits around their host stars and are older than 3 Gyr based on stellar isochrone models of the stars. TOI-569 is one of two slightly evolved stars known to host a transiting BD (the other being KOI-415). TOI-1406b is one of three known transiting BDs to occupy the mass range of 40-50 MJ and one of two to have a circular orbit at a period near 10 days (with the first being KOI-205b). Both BDs have reliable ages from stellar isochrones, in addition to their well-constrained masses and radii, making them particularly valuable as tests for substellar isochrones in the BD mass-radius diagram