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Plant pathogens cause significant losses to agricultural yields and increasingly threaten food security1, ecosystem integrity and societies in general2,3,4,5. Xylella fastidiosa is one of the most dangerous plant bacteria worldwide, causing several diseases with profound impacts on agriculture and the environment6. Primarily occurring in the Americas, its recent discovery in Asia and Europe demonstrates that X. fastidiosa’s geographic range has broadened considerably, positioning it as a reemerging global threat that has caused socioeconomic and cultural damage7,8. X. fastidiosa can infect more than 350 plant species worldwide9, and early detection is critical for its eradication8. In this article, we show that changes in plant functional traits retrieved from airborne imaging spectroscopy and thermography can reveal X. fastidiosa infection in olive trees before symptoms are visible. We obtained accuracies of disease detection, confirmed by quantitative polymerase chain reaction, exceeding 80% when high-resolution fluorescence quantified by three-dimensional simulations and thermal stress indicators were coupled with photosynthetic traits sensitive to rapid pigment dynamics and degradation. Moreover, we found that the visually asymptomatic trees originally scored as affected by spectral plant-trait alterations, developed X. fastidiosa symptoms at almost double the rate of the asymptomatic trees classified as not affected by remote sensing. We demonstrate that spectral plant-trait alterations caused by X. fastidiosa infection are detectable previsually at the landscape scale, a critical requirement to help eradicate some of the most devastating plant diseases worldwide.

In autumn 2013, the presence of Xylella fastidiosa , a xylem-limited Gram-negative bacterium, was detected in olive stands of an area of the Ionian coast of the Salento peninsula (Apulia, southern Italy), that were severely affected by a disease denoted olive quick decline syndrome (OQDS). Studies were carried out for determining the involvement of this bacterium in the genesis of OQDS and of the leaf scorching shown by a number of naturally infected plants other than olive. Isolation in axenic culture was attempted and assays were carried out for determining its pathogenicity to olive, oleander and myrtle-leaf milkwort. The bacterium was readily detected by quantitative polymerase chain reaction (qPCR) in all diseased olive trees sampled in different and geographically separated infection foci, and culturing of 51 isolates, each from a distinct OQDS focus, was accomplished. Needle-inoculation experiments under different environmental conditions proved that the Salentinian isolate De Donno belonging to the subspecies pauca is able to multiply and systemically invade artificially inoculated hosts, reproducing symptoms observed in the field. Bacterial colonization occurred in prick-inoculated olives of all tested cultivars. However, the severity of and timing of symptoms appearance differed with the cultivar, confirming their differential reaction.

MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.

Cell Painting is an image-based assay that offers valuable insights into drug mechanisms of action and off-target effects. However, traditional feature extraction tools such as CellProfiler are computationally intensive and require frequent parameter adjustments. Inspired by recent advances in AI, we trained self-supervised learning (SSL) models DINO, MAE, and SimCLR on a subset of the JUMP Cell Painting dataset to obtain powerful representations for Cell Painting images. We assessed these SSL features for reproducibility, biological relevance, predictive power, and transferability to novel tasks and datasets. Our best model (DINO) surpassed CellProfiler in drug target and gene family classification, significantly reducing computational time and costs. DINO showed remarkable generalizability without fine-tuning, outperforming CellProfiler on an unseen dataset of genetic perturbations. In bioactivity prediction, DINO achieved comparable performance to models trained directly on Cell Painting images, with only a small gap between supervised and self-supervised approaches. Our study demonstrates the effectiveness of SSL methods for morphological profiling, suggesting promising research directions for improving the analysis of related image modalities.

The geological map of Piemonte Region (Italy) is a graphic representation of the geology of the region, grounded on a large geodatabase, that can be also browsed as an interactive scalable map (GeoPiemonte Map) using a WebGIS application. The Map, produced at 1:250,000 scale, is the first original release of the 'GeoPiemonte Map' project. The geological data represented on the map derive from a thorough revision of available geological maps and literature, integrated with unpublished original data. The revision and harmonisation of existing and new data have been based on explicit criteria used for the classification of geologic units and their representation on the Map. These criteria firstly aimed at providing a lithostratigraphic, hierarchic subdivision of Piemonte geologic units and describing them using shared concepts and vocabularies, consistent with IUGS Descriptive Standards for the Geosciences.

MicroRNA-145-5p (miR-145) has been reported to regulate multiple oncogenes and is considered a tumor suppressor. However, it remains unknown whether the level of plasma miR-145 can serve as a risk biomarker for future cancer. Using a population-based cohort (n = 1740) derived from the Trøndelag Health Study (HUNT), we investigated whether plasma miR-145 levels were associated with (1) first life-time cancer, (2) cancer stage at diagnosis, and (3) 2-year all-cause mortality after cancer diagnosis. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Our findings showed that individuals in the highest quartile of plasma miR-145 levels had a 44% increased risk of developing cancer compared to those in the lowest quartile, independent of age, sex, body mass index, or smoking status (HR 1.44, 95% CI 1.03–2.00 p < 0.05). However, no association was observed between quartiles of miR-145 levels and the risk of being diagnosed with a metastatic cancer, or the risk of 2-year mortality after cancer diagnosis. Our findings suggest that high plasma miR-145 levels are associated with increased cancer risk without affecting the severity of the cancer at diagnosis or affecting the short-term prognosis.

How big should ventilation openings be in ventilated attics? In Denmark, guidelines describe what is sufficient to remove excess moisture penetrating through the ceiling. These guidelines are based on many years of experience. An important parameter is the tightness of the ceiling. With current regulations for the airtightness of buildings, convection through the ceiling is reduced compared to older buildings. Therefore, it is relevant to review these old rules of thumb and maybe revise them. In this two-year study, tests with different sizes of ventilation openings were conducted in a test house with 18 separate ventilated attics and airtight ceilings. One third of the attics were ventilated according to the guidelines, one third’s ventilation was reduced by one third and the last third had 50 % ventilation of the recommendations. Hourly measurements of temperature and relative humidity in the attics were conducted. Rafters in the attics were tested for mould growth. Six different types of insulation systems were used in the attics (with and without a vapour barrier, different insulation materials, and insulation thickness), therefore, the study also includes these differences. Earlier investigations, with full ventilation in all attics, showed no significant hygrothermal differences between them; consequently, it was assumed that the amount of ventilation would be decisive for the hygrothermal performance. This study follows up on this assumption. Results show little differences between the attics, mainly that having a vapour barrier becomes more important with reduced ventilation, and the insulation thickness and thereby U-value is of less importance. Reducing the requirements for ventilation of attics could be relevant, provided that the ceiling is airtight.

Background Gene fusions exist with low prevalence in colorectal cancer (CRC), and the clinical utility of fusion testing in advanced CRC remains unclear. We sought to identify oncogenic fusions in patients with advanced CRC using a fusion partner-agnostic circulating tumor DNA (ctDNA) assay to better understand their clinical relevance. Methods We performed a retrospective analysis using de-identified data from 18,558 patients with advanced CRC who underwent ctDNA next-generation sequencing with Guardant360 ® from 2017 to 2022. These samples were subsequently reanalyzed with a partner-agnostic bioinformatics method to identify both clonal and non-clonal fusions. We analyzed for associations between fusions and MSI-H status, as well prior EGFR-directed therapy signature. Results Fusions were identified in 221 (1.3%) of CRC patients analyzed. 193 patients had 258 activating fusions, while 28 patients had fusions of uncertain significance. Among patients with activating fusions, there were 18 clonal fusions (7%) and 240 (93%) subclonal fusions. Clonal fusions were more common in patients with MSI-H status, and subclonal fusions were associated with prior EGFR exposure signature. Conclusions Among patients with advanced CRC, partner-agnostic ctDNA fusion detection is possible and improves identification as a blood-based approach by extension of fusion calling partners. Detection of fusions in the ctDNA may provide rationale for potential therapeutic strategies according to clonality as informed by the ctDNA, whereas subclonal fusions may play a role in acquired resistance to EGFR inhibitors in KRAS/NRAS/BRAF wild−type tumors.

Background: Tyrosine kinase inhibitors (TKI) such as sunitinib and pazopanib display their efficacy in a variety of solid tumours. However, their use in therapy is limited by the lack of evidence about the ability to induce cell death in cancer cells. Our aim was to evaluate cytotoxic effects induced by sunitinib and pazopanib in 5637 and J82 bladder cancer cell lines. Methods: Cell viability was tested by MTT assay. Autophagy was evaluated by western blot using anti-LC3 and anti-p62 antibodies, acridine orange staining and FACS analysis. Oxygen radical generation and necrosis were determined by FACS analysis using DCFDA and PI staining. Cathepsin B activation was evaluated by western blot and fluorogenic Z-Arg-Arg-AMC peptide. Finally, gene expression was performed using RT–PCR Profiler array. Results: We found that sunitinib treatment for 24 h triggers incomplete autophagy, impairs cathepsin B activation and stimulates a lysosomal-dependent necrosis. By contrast, treatment for 48 h with pazopanib induces cathepsin B activation and autophagic cell death, markedly reversed by CA074-Me and 3-MA, cathepsin B and autophagic inhibitors, respectively. Finally, pazopanib upregulates the α -glucosidase and downregulates the TP73 mRNA expression. Conclusion: Our results showing distinct cell death mechanisms activated by different TKIs, provide the biological basis for novel molecularly targeted approaches.

Inhibition of bromodomain and extraterminal motif (BET) proteins such as BRD4 bears great promise for cancer treatment and its efficacy has been frequently attributed to Myc downregulation. Here, we use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor. Although JQ1 led to widespread eviction of BRD4 from chromatin, its effect on gene transcription was limited to a restricted set of genes. This was unlinked to Myc downregulation or its chromatin association. Yet, JQ1-sensitive genes were enriched for Myc and E2F targets, were expressed at high levels, and showed high promoter occupancy by RNAPol2, BRD4, Myc and E2F. Their marked decrease in transcriptional elongation upon JQ1 treatment, indicated that BRD4-dependent promoter clearance was rate limiting for transcription. At JQ1-insensitive genes the drop in transcriptional elongation still occurred, but was compensated by enhanced RNAPol2 recruitment. Similar results were obtained with other inhibitors of transcriptional elongation. Thus, the selective transcriptional effects following JQ1 treatment are linked to the inability of JQ1-sensitive genes to sustain compensatory RNAPol2 recruitment to promoters. These observations highlight the role of BET proteins in supporting transcriptional elongation and rationalize how a general suppression of elongation may selectively affects transcription.