julilili42/papers huggingface dataset:
Stylolites in Carbonate Rocks: Morphological Variability According to the Host Rock Texture
2025-01-29

Stylolites are ubiquitous structures in carbonates that present a variety of morphologies. Besides being important structures in terms of rock compaction and deformation, stylolites control limestone permeability, which is influenced by their morphology and arrangement in connected networks. This study characterizes stylolite morphological parameters, such as length, thickness, filling by insoluble material, spacing and connectivity, to provide quantitative data on the relationships between stylolite morphology and carbonate host rock textures. A collection of thin sections from a variety of lithologies and geological settings was analyzed, showing that the stylolite length, thickness and morphology are interrelated and are controlled by the host rock textures. The results show that stylolite linearity, calculated as the ratio between the straight length and the length measured along the stylolite trace, varies according to the stylolite type. Higher stylolite thickness is observed in mud-dominated textures compared to grain-dominated ones but is independent of the stylolite type. There is no clear trend in terms of the amount of insoluble material collected by the stylolites and the rock texture or stylolite type. Analysis of stylolite spacing reveals that heterogeneity in grain size, grain sorting and composition controls stylolite formation.
The novel p.A30G SNCA pathogenic variant in Greek patients with familial and sporadic Parkinson's disease
2025-01-29

Abstract Background The p.A53T variant in the SNCA gene was considered, until recently, to be the only SNCA variant causing familial Parkinson's disease (PD) in the Greek population. We identified a novel heterozygous p.A30G (c.89 C&gt;G) SNCA pathogenic variant in five affected individuals of three Greek families, leading to autosomal dominant PD. This study aims to further explore the presence and phenotypic expression of this variant in the Greek PD population. Methods Restriction fragment length polymorphism (RFLPs) was used for genotyping of 664 Greek PD cases. Detailed clinical information was obtained for the carriers and p.A30G‐positive samples underwent haplotype analysis. Results We identified 10 additional p.A30G‐positive PD patients (1.5%), of whom 4 were sporadic cases (0.9%). They manifested typical Parkinsonian motor dysfunction, with a mean age of onset of 51.7 years (range: 33–62) and a broad spectrum of non‐motor symptoms. The absence of affected first degree relatives in four out of ten index cases, and the presence of a phenocopy in an additional family, suggest that the p.A30G variant manifests reduced penetrance. The common haplotype among the p.A30G carriers confirmed a founder effect. Furthermore, two asymptomatic carriers were identified, with possible premotor manifestations. Conclusions These findings underscore that the p.A30G SNCA pathogenic variant represents an important, albeit rare, cause of genetic PD in the Greek population. This is the first time in which a genetic synucleinopathy, with a variant in the SNCA gene, is clearly linked to an appreciable frequency of sporadic PD in a particular population.
Oxidation state of bioavailable dissolved organic matter influences bacterioplankton respiration and growth efficiency
2025-01-29

Oxygen consumption by oceanic microbes can predict respiration (CO<sub>2</sub> production) but requires an assumed respiratory quotient (RQ; ΔO<sub>2</sub>/ΔCO<sub>2</sub>). Measured apparent RQs (ARQs) can be impacted by various processes, including nitrification and changes in dissolved organic matter (DOM) composition, leading to discrepancies between ARQ and actual RQ. In DOM remineralization experiments conducted in the eastern North Atlantic Ocean, ARQs averaged 1.39 ± 0.14, similar to predictions for complete consumption of plankton biomass. DOM removed with an elevated nominal oxidation state (i.e., more oxidized DOM), as detected by liquid chromatography-tandem mass spectrometry, coincided with increased hydrolyzable amino acid removal, increased ARQs and bacterioplankton respiration (BR), and a decreased bacterioplankton growth efficiency (BGE). Across experiments, evidence emerged that nitrification and DOM partial oxidation, driven in part by bacterioplankton members of OM43, SAR92 and Rhodobacteraceae, can elevate BR relative to bacterioplankton consumption of plankton-derived carbon. These rare synoptic measurements of interrelated variables reveal complex biochemical and cellular processes underlying variability in large-scale CO<sub>2</sub> production estimates.
Authenticity, Landscape and Tourism
2025-01-29

Both tourism and landscape academia heavily and passionately debate the authentic nature of both destination experiences and appearances. This paper attempts to bridge the gap between the concept of authenticity in landscape research and that in tourism studies. Using the landscape-related derivation of Popper's three world theory, the authors analyse various tourism and landscape-related phenomena that are typically used to determine authenticity in the two disciplines. As a result, they conclude that there is no such thing as an objectively authentic tourist experience, just as there is no such thing as an objectively authentic landscape. The appreciation of each is attained through the eyes and the perspective of the viewer and ultimately leads to a (social) construction of the authentic.
Comparison of specialist ataxia centres with non-specialist services in terms of care access and organisation, health services resource utilisation and costs in Germany using patient-reported data
2025-01-29

This study provides useful information about ataxia patient care pathways in Germany, with higher patients' satisfaction in SAC compared to non-SAC, without a significant difference in costs. The findings can be used to change policy for better care for people with these rare complex neurological diseases.
Ancient genomics and the origin, dispersal, and development of domestic sheep
2025-01-30

The origins and prehistory of domestic sheep ( Ovis aries ) are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate. Although the first European sheep flocks derive from Türkiye, in a notable parallel with ancient human genome discoveries, we detected a major influx of Western steppe–related ancestry in the Bronze Age.
Glucocorticoid receptor suppresses GATA6-mediated RNA polymerase II pause release to modulate classical subtype identity in pancreatic cancer
2025-01-30

Background Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a 5-year survival rate of 12%. It has two major molecular subtypes: classical and basal, regulated by the master transcription factors (MTFs) GATA6 and ΔNp63, respectively. Objective This study sought to uncover the transcriptional regulatory mechanisms controlling PDAC subtype identity. Design We integrated primary tumour single-cell RNA-seq, patient-derived xenograft RNA-seq and multispectral imaging to identify MTF-dependent, subtype-specific markers. We created subtype-specific fluorescent reporter systems and conducted drug screenings to find actionable targets. We analysed chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac), MTFs (GATA6, ΔNp63), RNA polymerase II (Pol II), H3K4me3-anchored chromatin topology (HiChIP) and nascent RNA capture sequencing (PRO-seq). Additionally, we used nuclease-dead Cas9 (dCas9) to manipulate transcriptional regulatory mechanisms. Results Our approach identified glucocorticoid receptor (GR) agonists as agents that suppress the classical transcriptional programme by interacting with GATA6. GATA6 regulates classical-specific transcription through promoter-proximal pause release. Depletion of GATA6 increased Pol II occupancy at GATA6-bound enhancers and transcriptional start sites, stabilising enhancer–promoter interactions. Artificially inducing pausing at GATA6-bound enhancers with dCas9 abrogated target gene expression and induced pausing at both the enhancer and target gene promoter. Conversely, in basal PDAC ΔNp63 promotes Pol II recruitment and stabilises enhancer–promoter interactions. Conclusion This study provides new insights into the transcriptional control and role of GR agonists in controlling PDAC molecular subtype identity.
OpenMS WebApps: Building User-Friendly Solutions for MS Analysis
2025-01-30

Liquid chromatography-mass spectrometry (LC-MS) is an indispensable analytical technique in proteomics, metabolomics, and other life sciences. While OpenMS provides advanced open-source software for MS data analysis, its complexity can be challenging for nonexperts. To address this, we have developed OpenMS WebApps, a framework for creating user-friendly MS web applications based on the Streamlit Python package. OpenMS WebApps simplifies MS data analysis through an intuitive graphical user interface, interactive result visualizations, and support for both local and online execution. Key features include workspace management, automatic generation of input widgets, and parallel execution of tools, resulting in high performance and ready-to-use solutions for online and local deployment. This framework benefits both researchers and developers: scientists can focus on their research without the burden of complex software setups, and developers can rapidly create and distribute custom WebApps with novel algorithms. Several applications built on the OpenMS WebApps template demonstrate its utility across diverse MS-related fields, enhancing the OpenMS ecosystem for developers and a wider range of users. Furthermore, it integrates seamlessly with third-party software, extending its benefits to developers beyond the OpenMS community.
One-day dual-tracer examination in neuroendocrine neoplasms: a real advantage of low activity LAFOV PET imaging
2025-01-30

Abstract Purpose Somatostatin receptor (SSTR)-PET is crucial for effective treatment stratification of neuroendocrine neoplasms (NENs). In highly proliferating or poorly differentiated NENs, dual-tracer approaches using additional [ 18 F]FDG PET can effectively identify SSTR-negative disease, usually requiring separate imaging sessions. We evaluated the feasibility of a one-day dual-tracer imaging protocol with a low activity [ 18 F]FDG PET followed by an SSTR-PET using the recently introduced [ 18 F]SiFA lin -TATE tracer in a long axial field-of-view (LAFOV) PET/CT scanner and its implications in patient management. Methods Twenty NEN patients were included in this study. Initially, a low activity [ 18 F]FDG PET was performed (0.5 ± 0.01 MBq/kg; PET scan 60 min p.i.). After 4.2 ± 0.09 h after completion of the [ 18 F]FDG PET, a standard activity of [ 18 F]SiFA lin -TATE was administered (3.0 MBq/kg; PET scan 90 min p.i.). To ensure the quantification accuracy of the second scan, we evaluated the potential impact of residual [ 18 F]FDG activity by segmenting organs with minimal physiological SSTR-tracer uptake, such as the brain and myocardium, and assessing the activity concentrations (ACTs) of tumor lesions. Residual tumor lesion ACTs of [ 18 F]FDG were calculated by factoring fluorine-18 decay, identifying a maximum residual ACT of 15% (R15%). To account for increased [ 18 F]FDG trapping over time, higher residual ACTs of 20% (R20%) were considered. These simulated [ 18 F]FDG ACTs were compared with those measured in the second PET scan with [ 18 F]SiFA lin -TATE. The influence of the dual-tracer PET/CT results on therapeutic strategies was evaluated. Results [ 18 F]FDG cerebral uptake significantly decreased in the subsequent SSTR-PET (mean uptake [ 18 F]FDG: SUV mean 6.0 ± 0.4; mean uptake in [ 18 F]SiFA lin -TATE PET: SUV mean 0.2 ± 0.01; p &lt; 0.0001); with similar results recorded for the myocardium. Simulated residual [ 18 F]FDG ACTs represented only a minimal percentage of ACTs measured in the tumor lesions from the second PET scan (R15%: mean 5.2 ± 0.9% and R20%: mean 6.8 ± 1.2%), indicating only minimal residual activity of [ 18 F]FDG that might interfere with the second PET scan using [ 18 F]SiFA lin -TATE and preserved semi-quantification of the latter. Dual-tracer PET/CT findings directly influenced changes in therapy plans in eleven (55%) of the examined patients. Conclusion LAFOV PET scanners enable a one-day dual-tracer protocol, providing diagnostic image quality while preserving the semi-quantification of two 18 F-labeled radiotracers, potentially simplifying the assessment of tumor biology and improving the clinical patient management while reducing logistical challenges. Additionally, low-activity PET imaging facilitates one-day dual-tracer PET examinations.
GlnA3 Mt is able to glutamylate spermine but it is not essential for the detoxification of spermine in Mycobacterium tuberculosis
2025-01-30

ABSTRACT Mycobacterium tuberculosis is well adapted to survive and persist in the infected host, escaping the host’s immune response. Since polyamines such as spermine, which are synthesized by infected macrophages, are able to inhibit the growth of M. tuberculosis , the pathogen needs strategies to cope with these toxic metabolites. The actinomycete Streptomyces coelicolor , a close relative of M. tuberculosis, makes use of a gamma-glutamylation pathway to functionally neutralize spermine. We therefore considered whether a similar pathway would be functional in M. tuberculosis . In the current study, we demonstrated that M. tuberculosis growth was inhibited by the polyamine spermine. Using in vitro enzymatic assays we determined that GlnA3 Mt (Rv1878) possesses genuine gamma-glutamylspermine synthetase catalytic activity. We further showed that purified His-Strep-GlnA3 Mt , as well as native GlnA3 Mt , prefer spermine as a substrate over putrescine, cadaverine, spermidine, or other monoamines and amino acids, suggesting that GlnA3 Mt may play a specific role in the detoxification of the polyamine spermine. However, the deletion of the glnA3 gene in M. tuberculosis did not result in growth inhibition or enhanced sensitivity of M. tuberculosis in the presence of high spermine concentrations. Gene expression analysis of spermine-treated M. tuberculosis revealed no difference in the level of glnA3 Mt expression relative to untreated cells, whereas a gene encoding a previously characterized efflux pump (Mmr; rv3065 ) was significantly upregulated. This suggests that bacterial survival under elevated spermine concentrations can not only be achieved by detoxification of spermine itself but also by mechanisms resulting in decreased spermine levels in the bacteria. IMPORTANCE Upon Mycobacterium tuberculosis infection macrophages synthesize the polyamine spermine, which at elevated concentrations is toxic for M. tuberculosis . Based on our investigations of spermine resistance in the closely related actinomycete Streptomyces coelicolor , we hypothesized that the glutamylspermine synthetase GlnA3 may be responsible for the resistance of M. tuberculosis against toxic spermine. Here we show that GlnA3 Mt can indeed covalently modify spermine via glutamylation. However, GlnA3 Mt is probably not the only resistance mechanism since a glnA3 null mutant of M. tuberculosis can survive under spermine stress. Gene expression studies suggest that an efflux pump may participate in resistance. Thus a combination of GlnA3 Mt and specific efflux pumps acting as putative spermine transporters may constitute an active spermine-detoxification system in M. tuberculosis .
Dopaminergic Mechanisms of Cognitive Flexibility: An [18F]Fallypride PET Study
2025-01-30

Cognitive flexibility is the ability to appropriately adapt one's thinking and behavior to changing environmental demands and is conceptualized as an aspect of executive function. The dopamine system has been implicated in cognitive flexibility; however, a direct, that is, neurochemical, link to cognitive flexibility has not been shown yet. The aim of this study was, therefore, to investigate how cognitive flexibility is mediated by dopaminergic signaling in the ventromedial prefrontal cortex (vmPFC). <b>Methods:</b> Eighteen participants were measured in a PET study with 174 ± 12 MBq of the D<sub>2/3</sub> receptor ligand [<sup>18</sup>F]fallypride in a block design with 2 parts. While participants processed 2 tasks sequentially without rule switching on a computer screen in the first part of the PET scan, they had to flexibly switch between the 2 task rules after 100 min after injection in the second part. Dopamine release (γ) was quantified using the linearized simplified reference region model contrasting the 2 task blocks (switching vs. no-switching/baseline). <b>Results:</b> The statistical analysis of the parametric γ-images showed that the increased cognitive demand during task switching induced a displacement of the D<sub>2/3</sub> receptor ligand [<sup>18</sup>F]fallypride in the vmPFC (maximum T value = 13.8; cluster size: 528 voxels; familywise error rate-corrected <i>P</i> < 0.001; mean γ = 0.022 ± 0.006 min<sup>-1</sup>). Furthermore, a correlation between behavioral switch costs and vmPFC [<sup>18</sup>F]fallypride displacement suggested that participants showing greater dopamine release were more efficient in task switching. <b>Conclusion:</b> To our knowledge, this is the first experimental PET study to show direct involvement of dopamine in the vmPFC in a task-switching paradigm, confirming model assumptions about the neurochemical basis of cognitive flexibility.
CO2 Reduction on Liquid GaInSn‐Metal: Dynamics of the Electrode–Electrolyte Interface
2025-01-30

Abstract Post‐transition liquid metal (LM) alloys are of increasing interest for the electro‐reduction of CO 2 . Besides avoiding coking effects, they often exhibit an electric field‐induced accumulation of elements at their interface, which can be used to tune catalytic activity and product selectivity. However, mechanistic insights into these systems remain sparse. In this study, we investigate the ternary GaInSn alloy in DMF‐based electrolyte. We demonstrate that even small amounts of water in DMF significantly increase the CO 2 reduction rate. Under optimized conditions (2 M water in DMF at −2.7 V versus Ag/Ag + ), the overall current density is approximately −3 mA/cm 2 , two orders of magnitude higher than in anhydrous electrolysis. The Faradaic efficiency for HCOOH and CO production is around 60% and 30%, respectively, whereas the competing hydrogen evolution remains a minor side product. Analysis of the electrolyte after CO 2 electrolysis reveals varying amounts of expelled tin and gallium. This suggest that an enrichment of the interface in tin may be responsible for the high selectivity toward HCOOH. Our study provides a better mechanistic understanding of CO 2 reduction on GaInSn and shows that the dynamic elemental composition should always be considered for the interpretation of experimental results.
Neuronal mechanisms enhancing selectivity of the innate number sense via learning
2025-01-30

Abstract In their feature article, Lorenzi et al. (2025) compiled extensive biological evidence on the ontogenetic origins of the number sense. Drawing on both behavioral and neurobiological data, they convincingly argue that the “number sense” is fundamentally innate and present from birth in numerically competent animals, including humans. At the same time, the authors acknowledge the role of learning and experience in shaping numerical cognition. This commentary builds on the idea of learning-induced changes to the number sense, extending the concept of an innate number sense to one that is modifiable through learning and experience. It summarizes evidence from single-neuron recordings and proposes neurophysiological mechanisms underlying these learning-induced changes in numerical cognition.
Extended receptor repertoire of an adenovirus associated with human obesity
2025-01-30

Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach. The HAdV-D36 fiber knob domain (FK), which mediates the primary attachment of many HAdVs to host cells, has a significantly elongated DG loop that alters known binding interfaces for established adenovirus receptors such as the coxsackie- and adenovirus receptor (CAR) and CD46. Our data suggest that HAdV-D36 attaches to host cells using a versatile receptor pool comprising sialic acid-containing glycans and CAR. Sialic acids are recognized at the same binding site used by other HAdVs of species D such as HAdV-D37. Using glycan microarrays, we demonstrate that HAdV-D36 displays a binding preference for glycans containing a rare sialic acid variant, 4- O ,5- N -diacetylneuraminic acid, over the more common 5- N -acetylneuraminic acid. To date, this sialic acid variant has not been detected in humans, although it can be synthesized by various animal species, including a range of domestic and livestock animals. Taken together, our results indicate that HAdV-D36 has evolved to recognize a specialized set of primary attachment receptors that are different from known HAdV types and coincides with a unique host range and pathogenicity profile.
JNK Inhibition Overcomes Resistance of Metastatic Tetraploid Cancer Cells to Irradiation-Induced Apoptosis
2025-01-30

Tetraploidy is a condition in which the entire set of chromosomes doubles, most often due to errors during cell division. Tetraploidy can lead to genomic instability and significant consequences, in particular metastasis and treatment failure in tumours, including radiotherapy. The development of new strategies to sensitise these cells to treatment is of great importance. In our study, we investigated the in vitro combination of chemical treatment with the kinase inhibitor SP600125 and irradiation on diploid versus metastatic tetraploid RKO colon cancer clones. We assessed mitochondrial transmembrane potential, cell cycle and subG1 population by flow cytometry and performed clonogenic assays to evaluate cell sensitivity. We found that the combination overcomes irradiation resistance in metastatic tetraploid clones. To identify the main pathway involved in cell sensitivity, we screened the Harvard Medical School KINOMEscan library and performed a gene ontology biological process analysis. We found that the major kinases inhibited by SP600125 were ANKK1, BIKE, IKKA, JNK1, MP2K3, MP2K4, MKNK2, MYLK, PLK4, RPS6KA4(Kin,Dom,1), MYLK4 and TTK, and the pathways involved in clone sensitivity were DNA damage repair, radiation resistance and apoptosis, through JNK pathway inhibition. Finally, our main finding was that combined treatment with SP600125 and radiotherapy reduced the resistance of metastatic tetraploid cells to treatment, essentially by inhibiting the JNK pathway. This result supports a promising anti-cancer strategy to overcome the resistance of tetraploid cancer cells to irradiation.