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Europe must safeguard climate data following NASA cuts
Author Correction: Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer
Expert evaluation of ChatGPT accuracy and reliability for basic celiac disease frequently asked questions
Enhanced ethylene/ethane selectivity of PI membrane with functionalized zeolite addition
Mapping and engineering RNA-driven architecture of the multiphase nucleolus
A fluorescence lifetime-based FLIM-timer for measuring the protein turnover of transcription factor Nrf2 in live cells
Abstract Measuring protein turnover in cells has been greatly assisted by fluorescent timers (FT). However, FT quantification requires relatively high fluorescence intensity samples, prohibiting their use for proteins with low or non-uniform expression like transcription factor Nrf2, the master regulator of redox homeostasis. To visualise changes in stability/turnover of Nrf2, we constructed a genetically encoded tag combining sfGFP and mCherry and used intensity-independent Fluorescence Lifetime Imaging (FLIM) to measure Förster Resonance Energy Transfer (FRET) within the tag (named FLIM-timer). We show that the ability of mCherry to act as a FRET-acceptor develops as the protein matures, allowing the use of FLIM-FRET as a readout of the FLIM-timer. FLIM-timer-tagged Nrf2 allowed to observe differences in its turnover between cellular compartments with equal precision in regions of high and low brightness. The reduction in fluorescence lifetime of FLIM-timer-Nrf2 confirmed its stabilisation by sulforaphane. Depletion of a degron for either Keap1-Cul3 or SCFβ-TrCP-mediated degradation decreased the fluorescence lifetime of Nrf2-FLIM-timer. FLIM-timer labelled cyclin B was also successfully used to track its destabilisation during mitotic exit. Thus, FLIM-timer methodology increases the FT applicability for visualisation and quantification of protein turnover, expanding it to cells with low and variable levels of any protein of interest.
Space- and object-based attention in patients with a single hemisphere following childhood resection
Trump’s chief science adviser faces a storm of criticism: what's next?
Inter- and intra-observer agreement in ultrasound diagnosis of steatotic liver disease: implications for screening in resource-limited settings
Abstract Steatotic liver disease (SLD), which is associated with increased risk of cancer-related mortality, needs timely and cost-effective detection. Although liver biopsy remains the diagnostic gold standard, its invasiveness and high-cost limit widespread use. Ultrasound is a practical and affordable alternative. We evaluated inter- and intra-observer agreement for ultrasound-based diagnosis of SLD using images from the Chile Biliary Longitudinal Study (Chile BiLS), a cohort of women with gallstones. These women have a high burden of obesity and related metabolic disorders, putting them at higher risk for SLD. A radiologist (observer 1) reviewed a randomly selected subset of 425 baseline images and compared them with the original readings from Chile BiLS radiology technicians. To assess intra-observer reproducibility, observer 1 reanalyzed 34 blinded duplicates, and two Chile BiLS radiology technicians (observers 2 and 3) independently reviewed these images. Observer 2 then re-reviewed the 34 images to assess intra-observer agreement. Agreement was analyzed using kappa and percent agreement. Observer 1 had slight inter-observer agreement (kappa: 0.12; 95% CI 0.08–0.15, p < 0.001; percent agreement: 41.0%), while observers 2 and 3 showed fair agreement (kappa: 0.29: 95% CI 0.11–0.58, p < 0.05; percent agreement: 64.7% and kappa: 0.32: 95% CI 0.06–0.58, p < 0.05; percent agreement: 63.6%, respectively). Intra-observer agreement was moderate for observer 1 (kappa: 0.45; 95% CI 0.08–0.82, p < 0.05; percent agreement: 81.3%), and substantial for observer 2 (kappa: 0.64; 95% CI 0.37–0.90, p < 0.001; percent agreement: 81.8%). Our findings highlight variability in ultrasound interpretation, underscoring the necessity of inter- and intra-observer comparisons for optimal diagnosis and quality control to enhance diagnostic consistency in high-risk populations.
‘A whole body of health-equity research is being disappeared’ — why I resigned from the NIH
GRSF1 loss in THP-1 macrophages promotes senescence-associated transcription in neighboring fibroblasts
Abstract Immunosenescence, the age-associated decline in immune function, is accompanied by altered macrophage phenotypes and increased chronic inflammation. Here, we examined the role of the mitochondrial RNA-binding protein GRSF1 in regulating macrophage-driven inflammation and its impact on neighboring fibroblasts. We found that macrophages differentiated from GRSF1-deficient THP-1 monocytes, particularly M(IL-4 + IL-13) macrophages, displayed elevated IL6 mRNA expression levels and TNF-α secretion, without inducing overt senescence in macrophages themselves. Conditioned media from these macrophages triggered robust senescence-associated transcriptional changes in fibroblasts, including increased expression of IL6 , TNF , DPP4 , and IL8 , as well as elevated SA-β-gal activity. Notably, expression of NF-κB-regulated long noncoding RNAs, such as ANRIL and PACER , was also induced in fibroblasts, suggesting the engagement of an NF-κB-linked inflammatory program. These transcriptional responses were mitigated by red ginseng extract, an anti-inflammatory compound known to suppress TNF-α signaling. Collectively, our findings suggest that GRSF1 depletion in macrophages contributes to a paracrine inflammatory niche that promotes senescence-associated gene expression in surrounding cells.
Study how screen time affects circadian rhythms
Effect of tea manufacturing processes and cultivars on tea infusion color
Organs on chips could make biomedical research more equitable
Electron flow in hydrogenotrophic methanogens under nickel limitation
Abstract Methanogenic archaea are the main producers of the potent greenhouse gas methane1,2. In the methanogenic pathway from CO2 and H2 studied under laboratory conditions, low-potential electrons for CO2 reduction are generated by a flavin-based electron-bifurcation reaction catalysed by heterodisulfide reductase (Hdr) complexed with the associated [NiFe]-hydrogenase (Mvh)3–5. F420-reducing [NiFe]-hydrogenase (Frh) provides electrons to the methanogenic pathway through the electron carrier F420 (ref. 6). Here we report that under strictly nickel-limited conditions, in which the nickel concentration is similar to those often observed in natural habitats7–11, the production of both [NiFe]-hydrogenases in Methanothermobacter marburgensis is strongly downregulated. The Frh reaction is substituted by a coupled reaction with [Fe]-hydrogenase (Hmd), and the role of Mvh is taken over by F420-dependent electron-donating proteins (Elp). Thus, Hmd provides all electrons for the reducing metabolism under these nickel-limited conditions. Biochemical and structural characterization of Elp–Hdr complexes confirms the electronic interaction between Elp and Hdr. The conservation of the genes encoding Elp and Hmd in CO2-reducing hydrogenotrophic methanogens suggests that the Hmd system is an alternative pathway for electron flow in CO2-reducing hydrogenotrophic methanogens under nickel-limited conditions.