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E2F1 activates breast stromal fibroblasts and promotes their paracrine pro-carcinogenic effects

Museomics and morphological analyses of historical and contemporary peninsular Italian wolf (Canis lupus italicus) samples

Abstract After centuries of decline and protracted bottlenecks, the peninsular Italian wolf population has naturally recovered. However, an exhaustive comprehension of the effects of such a conservation success is still limited by the reduced availability of historical data. Therefore, in this study, we morphologically and genetically analyzed historical and contemporary wolf samples, also exploiting the optimization of an innovative bone DNA extraction method, to describe the morphological variability of the subspecies and its genetic diversity during the last 30 years. We obtained high amplification and genotyping success rates for tissue, blood and also petrous bone DNA samples. Multivariate, clustering and variability analyses confirmed that the Apennine wolf population is genetically and morphologically well-distinguishable from both European wolves and dogs, with no natural immigration from other populations, while its genetic variability has remained low across the last three decades, without significant changes between historical and contemporary specimens. This study highlights the scientific value of well-maintained museum collections, demonstrates that petrous bones represent reliable DNA sources, and emphasizes the need to genetically long-term monitor the dynamics of peculiar wolf populations to ensure appropriate conservation management actions.

Diagnostic classification in toxicologic pathology using attention-guided weak supervision and whole slide image features: a pilot study in rat livers

Machine learning integrated with in vitro experiments for study of drug release from PLGA nanoparticles

Integration of transcriptomics and metabolomics data revealed role of insulin resistant SNW1 gene in the pathophysiology of gestational diabetes

Retraction Note: A novel, bioactive and antibacterial scaffold based on functionalized graphene oxide with lignin, silk fibroin and ZnO nanoparticles

Exploring the genetic correlation and causal relationships between breast cancer and meningioma using bidirectional Mendelian randomization

Longer respiratory events in childhood obstructive sleep apnea syndrome constitute a trait of older children with excessive daytime sleepiness

Establishment of predictive models for head loss and filtration efficiency of pontoon mesh rotary filter based on dimension analysis

Users’ experiences of park accessibility and attractiveness based on online review analytics

Individualized models of social judgments and context-dependent representations

The relationship between perception and landscape characteristics of recreational places with human mental well-being

Abstract Being outdoors benefits both humans’ physical and mental well-being, but the reasons for this connection are difficult to pinpoint. This study examines 40 recreational areas to understand their individual characteristics’ impact on mental well-being. We interviewed 1184 visitors on their perception of the place and feeling of mental well-being. In a second survey, 49 participants were shown images of the areas to assess whether they perceived them in the same way as people on-site did. Biologists then evaluated the areas through bird and biotope surveys, also assessing various other landscape characteristics of the study areas. Analysis using a two-level multivariate GLM revealed that perceived naturalness and perceived bird diversity are significant predictors of improved mental well-being. On the flip side, mental well-being declines with increased human impact, as indicated by the amount of infrastructure and the Human Footprint Index value. Notably, perceived naturalness positively correlates with actual bird diversity (p = 0.005) and negatively with human impact (p = 0.006). A strong perception of birds enhances the mental well-being of greenspace visitors (p < 0.001), while a high birding specialization negatively affects recalled restoration (p = 0.014). The estimated restoration value (p = 0.001) and estimated beauty (p < 0.001) from the online survey correlate positively with emotions experienced on-site. The perception of naturalness in images aligns with on-site perception, suggesting pathways for future research and the design of recreational areas.

Symbolism itself does not improve memory for elements on the periodic table

Machine learning-random forest model was used to construct gene signature associated with cuproptosis to predict the prognosis of gastric cancer

ThyroNet-X4 genesis: an advanced deep learning model for auxiliary diagnosis of thyroid nodules’ malignancy

Sustainable hybrid systems for electric vehicle charging infrastructures in regional applications

Amyloidogenic immunoglobulin light chains disturb contractile function and calcium transients in a human cardiac spheroid model of light chain (AL) amyloidosis

Cryo-ET suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubules

The functional architecture of the long-lived neuronal microtubule (MT) cytoskeleton is maintained by various MT-associated proteins (MAPs), most of which are known to bind to the MT outer surface. However, electron microscopy (EM) has long ago revealed the presence of particles inside the lumens of neuronal MTs, of yet unknown identity and function. Here, we use cryogenic electron tomography (cryo-ET) to analyze the three-dimensional (3D) organization and structures of MT lumenal particles in primary hippocampal neurons, human induced pluripotent stem cell–derived neurons, and pluripotent and differentiated P19 cells. We obtain in situ density maps of several lumenal particles from the respective cells and detect common structural features underscoring their potential overarching functions. Mass spectrometry-based proteomics combined with structural modeling suggest that a subset of lumenal particles could be tubulin-binding cofactors (TBCs) bound to tubulin monomers. A different subset of smaller particles, which remains unidentified, exhibits densities that bridge across the MT protofilaments. We show that increased lumenal particle concentration within MTs is concomitant with neuronal differentiation and correlates with higher MT curvatures. Enrichment of lumenal particles around MT lattice defects and at freshly polymerized MT open-ends suggests a MT protective role. Together with the identified structural resemblance of a subset of particles to TBCs, these results hint at a role in local tubulin proteostasis for the maintenance of long-lived neuronal MTs.

Siponimod supports remyelination in the non-supportive environment

Abstract Inflammatory demyelination, a hallmark of multiple sclerosis (MS) lesions, leads to functional impairments and progressive axonal loss over time. Although remyelination is thought to protect axons, endogenous regenerative processes are often incomplete or fail entirely in many MS patients. While the precise reasons for remyelination failure remain unclear, repeated demyelination in previously affected white matter regions is a recognized contributing factor. In a previous study, we demonstrated that the sphingosine-1-phosphate modulator Siponimod ameliorates metabolic oligodendrocyte injury in an MS animal model. In this study, we explored the potential of Siponimod to enhance remyelination in a non-supportive environment. To this end, male mice were subjected to Cuprizone intoxication for seven weeks. From the onset of the fifth week, when oligodendrocyte progenitor cells begin to differentiate, mice were administered either a vehicle or Siponimod solution. Post-treatment, brain specimens were processed for (immune-) histochemical analyses. After four weeks of Cuprizone intoxication, staining intensities for various myelination markers, were significantly reduced. At the end of week seven, loss of myelin staining intensities was still pronounced, but anti-myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) expression was significantly higher in Siponimod- versus vehicle-treated mice. Consistent with this finding, densities of OLIG2+ oligodendrocytes significantly recovered in Siponimod-treated but not in vehicle-treated mice. This enhanced recovery was paralleled by the trend of lower densities of Ki67+ proliferating oligodendrocyte progenitor cells. Our findings suggest that Siponimod has modest pro-regenerative capacities, partly explaining the amelioration of disease progression in secondary progressive MS patients.

Art promotes exploration of negative content

Experiencing negative content through art has a unique power to transform our perceptions and foster engagement. While this idea has been widely discussed, empirical evidence is scarce, since experimental testing of art experiences poses significant challenges. Here, we aimed to fill this gap by quantifying and comparing individuals’ preference for engaging with art and nonart depicting matched negative content via two behavioral measures: the choice to engage vs. avoid and the duration of engagement. Across five studies (total N = 1,063), results revealed a preference for engaging with negative content through art as compared to nonart. Specifically, people more frequently chose to view negative art images, and looked at them for longer, as compared to photographs of similar content. To understand what underlies this preference for art, we examined the psychological impact of engaging with negative content through art and nonart depictions. Results showed that art experiences evoked higher aesthetic appreciation, while nonart gave the viewer a more realistic perspective and was emotionally more costly to engage with. Further, our analysis of engagement motives revealed that individuals were driven by expectations of aesthetic appreciation, thought-provocativeness, and an original perspective, both in art and nonart, while they were discouraged by emotional costs, even more strongly when engaging with nonart. These findings align with the idea of aesthetic distance, where art, as an abstraction of reality, facilitates exploration of negative content with less emotional costs and the prospect of aesthetic rewards.