julilili42/papers huggingface dataset:
Self-resistance mechanism to acyldepsipeptide antibiotics in the Streptomyces producer
2025-10-06

ABSTRACT Clp proteases are ubiquitous in bacteria and play an important role in regulatory proteolysis and in maintaining protein homeostasis within the bacterial cell. They consist of a tetradecameric, proteolytic ClpP core and associated AAA+ Clp-ATPases. The Clp system of Streptomyces is unusually complex, comprising up to five ClpP homologs (ClpP1–ClpP5) and three Clp-ATPases (ClpX, ClpC1, and ClpC2). Streptomycetes produce a plethora of secondary metabolites, including potent acyldepsipeptide (ADEP) antibiotics, which target ClpP. We have previously reported on the operation mode of the Streptomyces ClpP1P2 protease and identified a novel clpP gene (named clpP ADEP ) as a resistance determinant encoded near the ADEP biosynthesis gene cluster. However, the molecular function of ClpP ADEP remains enigmatic. Here, we report on the molecular self-resistance mechanism to ADEP via ClpP ADEP and its interaction with the Clp system in the ADEP producer Streptomyces hawaiiensis NRRL 15010. By combining cell-based and in vitro studies, we show that ClpP ADEP interferes with the formation of the ClpP1P2 complex and inhibits the proteolytic activity of ClpP1. Moreover, ClpP ADEP forms a functional complex with ClpP2 and Clp-ATPases. By these means, ClpP ADEP protects the producer cell against ADEP in a two-pronged approach. On the one hand, it prevents ADEP from corrupting ClpP1 to degrade delicate essential proteins and polypeptides. On the other hand, ClpP ADEP ensures the survival of the producer cells by maintaining the housekeeping function of the Clp protease in regulatory proteolysis. IMPORTANCE Acyldepsipeptide (ADEP) antibiotics kill bacteria using an unusual mechanism of action, that is, the multilayered deregulation and activation of ClpP, the proteolytic core of the bacterial Clp protease. ADEP is highly effective in killing Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Considering the elaborate mechanism of action of ADEP as well as the complexity of the essential Clp system in Streptomyces with up to five ClpP homologs as potential ADEP targets, the question arises: how does the producer ensure self-resistance in such a complex system? Here, we describe the molecular mechanism of self-resistance to ADEP in the producer Streptomyces hawaiiensis NRRL 15010, which is based on the presence of a phylogenetically distinct ClpP protein in the genome of the ADEP producer strain.
Neural complexity in preterm infants is predicted by developmental variables
2025-10-06

Neural complexity, measured as the entropy of noninvasively recorded electrophysiological signals, evolves with age in early infancy, differentiates between typical and atypical development, and likely serves as a surrogate marker of brain maturation. However, the reason for this evolution of neural entropy in early infant development remains unclear. To understand this evolution, we measured the proportion of time that the infant brain spent in a bursting pattern of activity and related this activity pattern to the neural complexity (i.e., entropy or entropy rate). Additionally, we sought to predict neural complexity using each infant’s gestational age and to replicate sex-related complexity differences previously reported in age-equivalent fetuses. Four distinct complexity estimator algorithms – Lempel-Ziv (LZ) complexity, multiscale entropy (MSE), complexity via state-space entropy rate (CSER), and context tree weighting (CTW) – were applied to 8-channel infant electroencephalogram (EEG) recordings in 28 preterm infants (27–34 weeks gestational age). To explore factors influencing signal complexity, we modeled relationships between complexity estimates, on the one hand, and spontaneous activity transients, gestational age, and sex, on the other hand. We calculated channel-averages for each complexity estimate separately, as derived either from entire EEG recordings or separately from burst and interburst periods. Our results suggest that increased EEG signal continuity with maturation may drive increases in neural complexity as quiescent periods subside. Additionally, our results largely recapitulate previous findings linking neural complexity to biological sex in third-trimester fetuses. We also observed unexpected differences between entropy rate results obtained using CSER (a newer algorithm) and older algorithms. These findings support further research into neural complexity as a potential predictor of clinical outcomes in infants at high risk for neurodevelopmental disorders.
Rydberg atom arrays as quantum simulators for molecular dynamics
2025-10-06

Rydberg atoms held in optical tweezer arrays combine vibrational and electronic degrees of freedom that can be coupled and manipulated at a microscopic level. This opens opportunities for the quantum simulation of artificial molecular systems and offers in particular a platform for probing complex vibronic dynamics in controlled settings with increasing complexity. Tailored interatomic interactions and electron-phonon couplings yield handles for designing electronic state manifolds, for studying structural transitions, and for exploring nonclassical vibrational states near molecular instabilities. Furthermore, this quantum simulator opens opportunities for testing and quantifying the validity of fundamental concepts, such as the Born-Oppenheimer approximation and quantum corrections to it.
MicroRNA-371a-3p Represents a Novel and Effective Diagnostic Marker for Testicular Germ Cell Tumours: A Real-World Prospective Comparison with Conventional Approaches
2025-10-06

Background/Objectives: Testicular germ cell tumours (GCT) have high cure rates, especially in early stages. MicroRNA-371a-3p (M371) has recently emerged as a highly sensitive biomarker for malignant GCTs, except teratoma. This study aimed to evaluate the diagnostic performance of M371-test in a real-life clinical setting, compared to conventional markers alpha-fetoprotein (AFP), lactate-dehydrogenase (LDH), and beta-human chorionic gonadotropin (β-HCG) in patients with suspected GCT. Methods: The study, approved by the Ethic-Committee of the Provincial Hospital of Bolzano (N.97-2021), included 91 M371-tests, performed from March 2021 to May 2025. A total of 75 patients had suspected GCT; 19 healthy males served as control. Serum levels of M371, AFP, LDH, and β-HCG were compared with final histopathological diagnosis. M371 was also assessed in controls to evaluate test performance. Secondary analyses investigated correlations between preoperative M371 levels and tumour size in non-metastatic patients, and between M371-levels and clinical stage in the entire GCT cohort. A cut-off of RQ &gt; 5 (relative quantification) was used to calculate sensitivity, specificity, and predictive values. Results: M371 showed a sensitivity of 90.9% and specificity of 89.3%, outperforming in terms of sensitivity AFP (20.4%/96.4%), LDH (40.9%/96.4%), and β-HCG (43.1%/100%). Positive predictive value (PPV) and negative predictive value (NPV) were 93.0% and 86.2%, respectively. Sensitivity was 95% for non-seminomas and 87.5% for seminomas. In non-metastatic patients, M371 levels correlated with tumour size and were significantly higher in advanced stages (median RQ 1128.35 vs. 98.36; p = 0.015). Conclusions: M371 showed excellent diagnostic performance, even for small tumours, supporting its clinical use. Further studies are needed to define its role in treatment planning and follow-up.
Time- and Temperature-Resolved Triplet Dynamics in Tungsten Iodide Clusters
2025-10-06

This study comprehensively investigates the excited-state dynamics of two tungsten iodide prototype clusters, [(W<sub>6</sub>I<sub>8</sub>)I<sub>6</sub>]<sup>2-</sup> and [(W<sub>6</sub>I<sub>8</sub>)(TFA)<sub>6</sub>]<sup>2-</sup> (TFA = trifluoroacetate), utilizing a combination of ultrafast transient absorption spectroscopy from 200 fs up to 400 μs and temperature-dependent emission spectroscopy from 4 to 340 K. Both clusters exhibit rapid intersystem crossing occurring within 6 ps, populating triplet states that subsequently deactivate through emission or dynamical bimolecular quenching involving molecular oxygen. The temperature-dependent emission behavior aligns well with a group-theoretical spin-sublevel model, indicating three distinct emissive sublevels. However, contrary to previous findings in molybdenum-based clusters, no additional splitting of the lowest triplet states was observed experimentally. Time-dependent density functional theory calculations highlight substantial excited-state geometrical distortions, suggesting limitations in sole group-theoretical descriptions. Instead, we propose a relativistic model with three thermally accessible excited-state geometries, each presenting three triplet sublevels.
Comprehensive Mitigation of Peripheral and Central Stress Responses by Nx4: Insights From EEG and Heart Rate Variability in Post‐Stress Resting State
2025-10-07

ABSTRACT Objective Stress from daily psychosocial challenges is a significant health concern with limited pharmacological treatment options. Psychosocial stress triggers distinct responses in the autonomic and central nervous systems, measurable via heart rate variability (HRV) and electroencephalogram (EEG). This post hoc analysis of clinical trial data explores the impact of the anti‐stress medication Neurexan (Nx4) on HRV and EEG signals, and their correlation in a resting state following acute psychosocial stress induction. Methods Data from the NEURIM trial (NCT02602275), a randomized, placebo‐controlled, double‐blind, cross‐over study, were utilized. Participants received Nx4 before exposure to ScanSTRESS, a psychosocial stress paradigm. EEG and photoplethysmogram data were collected at rest before and after stress exposure. Stress responsivity under both placebo and Nx4 conditions was evaluated through HRV and EEG signals. Results Psychosocial stress altered HRV parameters (increased LF/HF ratio, elevated Baevsky's Stress Index, reduced RMSSD) and EEG activity (decreased aperiodic offset, increased alpha power). Nx4 significantly mitigated stress‐induced changes in LF/HF ratio, Baevsky's Stress Index, and aperiodic offset. A significant correlation was observed between Nx4 effects on HRV and EEG activity. Conclusion Nx4 attenuates peripheral and central physiological stress responses, suggesting a comprehensive approach to mitigating stress responses in daily life.
A flipped classroom improves medical students’ skills how to manage medical emergencies—an intervention-control study
2025-10-07

Abstract Background Emergency medical skills must be mastered by every doctor. Early implementation of these skills in medical education is, therefore, essential. A form of realization is simulation-based training, which offers several advantages: it can be implemented at low threshold in undergraduate medical curricula, induces comparable stress levels to doctors in real-life situations and improves patient morbidity and mortality. Additionally, knowledge acquisition can be improved via e-learning. Teaching formats such as flipped classrooms have proven to be effective. However, it remains unclear whether the flipped classroom is also more effective than traditional classroom teaching in preparing students to apply emergency medicine competencies in realistic simulation scenarios. Therefore, this study aims to analyze the influence of an e-learning based flipped classroom approach combined with a simulation-based training on the acquisition of competencies in practical emergency measures compared to a classic classroom plus simulation course. Methods This prospective intervention-control study is based on a standardized, simulation-based training designed to increase undergraduate medical students’ skills in managing medical emergencies. Participants were assigned to one of two groups: the control group received classic classroom-based theoretical input prior to simulation training, while the study group followed a flipped classroom approach, completing the same theoretical content through e-learning modules. Duration of theoretical input and simulation-based training was identical for both groups. Outcomes were assessed using a formative OSCE, consisting of six emergency case scenarios, based on standardized checklists. Results 165 students participated in the study (86 Control group, 79 study group). Participants in the flipped classroom training group scored significantly higher in all six emergency case scenarios. Conclusion This study shows that an e-learning-based flipped classroom approach, when combined with simulation training and supported by well-designed instructional content, can improve the acquisition of practical emergency medicine skills compared to a traditional classroom format with identical simulation training.
Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma
2025-10-07

Abstract Enteropathy-associated intestinal T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) have distinctive clinical context, morphology, and immunophenotype. To characterize their genetic and molecular specificities, we compared 30 EATLs and 52 MEITLs by whole-exome, RNA and miRNA sequencing and DNA methylation profiling. Highly recurrent SETD2 loss-of-function alterations and frequent mutations of H3-3A/B consistently altering H3R2, implying deregulation of histone marks, were selectively found in MEITL. EATL instead harbored frequent mutations in TET2, ARID1A , and KMT2D . Highly prevalent JAK-STAT pathway mutations preferentially affected JAK3 and STAT5B in MEITL, and JAK1 and STAT3 in EATL. Half of EATLs contained disruptive mutations in HLA class I genes, impacting class I molecule expression. EATL containing more abundant macrophages was enriched in inflammatory response signatures, with upregulation of CD274, CXCL13 , and IDO1 transcripts, suggesting an immunosuppressive tumor microenvironment. CpGs hypomethylated in MEITL compared to EATL were enriched in promoter regions. Unsupervised analyses of mutations, transcription, and methylation profiles concordantly segregated EATLs from MEITLs. In summary, the distinctive genetic, epigenetic, and expression footprints of EATL and MEITL established by this study expand disease-defining features, have diagnostic implications, and provide a rationale for targeted therapies.
Impact of the Ligands’ Electronic Dipole Moment on Electrochemical p-Doping of CsPbBr3 Nanocrystals
2025-10-07

Lead halide perovskite nanocrystals (NCs) are promising materials for light-emitting diodes (LEDs) due to their wavelength tunability, narrow emission line width, and high photoluminescence quantum yield. Oftentimes, these devices suffer from charge carrier imbalance and reduced charge injection because as-synthesized NCs are covered by long aliphatic ligands. Here, we show a ligand exchange to small electron-withdrawing or electron-donating cinnamate ligands. We probe the influences of the ligands’ dipole moment on hole injection by photoluminescence spectroelectrochemistry (PL SEC). We find that hole injection into NCs covered by electron-withdrawing ligands is facilitated and that these NCs exhibit a superior LED performance. Our results emphasize the importance of kinetic hinderance for charge carrier injection into NC films, a feature that is more accurately derived by SEC compared to other techniques like photoelectron spectroscopy.
CDKL1 variants affecting ciliary formation predispose to thoracic aortic aneurysm and dissection
2025-10-07

Genetic factors are fundamental in the etiology of thoracic aortic aneurysm and dissection (TAAD), but the genetic cause is detected in only about 30% of cases. To define unreported TAAD-associated sequence variants, exome and gene panel sequencing was performed in 323 patients. We identified heterozygous CDKL1 variants [c.427T>C p.(Cys143Arg), c.617C>T p.(Ser206Leu), and c.404C>T p.(Thr135Met)] in 6 patients from 3 families with TAAD-spectrum disorders. CDKL1 encodes a protein kinase involved in ciliary biology. Amino acid substitutions were predicted to affect CDKL1 catalytic activity or protein binding properties. CDKL1 was expressed in vascular smooth muscle cells in normal and diseased human aortic wall tissue. Cdkl1 knockdown and transient knockout in zebrafish resulted in intersomitic vessel (ISV) malformations and aortic dilation. Co-injection of human CDKL1wildtype, but not CDKL1Cys143Arg and CDKL1Ser206Leu RNA, rescued ISV malformations. All variants affected CDKL1 kinase function and profiling data, and altered protein-protein binding properties, particularily with ciliary transport molecules. Expression of CDKL1 variants in heterologeous cells interfered with cilia formation and length, CDKL1 localization, and p38-MAPK and Vegf signaling. Our data suggest a role of CDKL1 variants in the pathogenesis of TAAD-spectrum disorders. The association between primary cilia dysregulation and TAAD expands our knowledge of the underlying molecular pathophysiology.
The Effect of Synthetic Cow Urine on Microorganisms and Their Potential Phosphorus Mining Activity in Rhizosphere and Bulk Soil
2025-10-07

ABSTRACT Background and aims Soil microbes adapt to varying nutrient inputs by modifying their utilization strategies, with root exudates and animal urine serving as key carbon (C) and nutrient sources in grasslands. Nonetheless, the specific mechanisms by which cow urine and root exudates influence microbial community and resource utilization remain elusive. This study investigates the differential effects of cow urine on microbial biomass, community composition and enzymatic activity in C‐rich (rooted) and C‐poor (vegetation‐free) soil. Methods A laboratory experiment was conducted using synthetic cow urine applied to a Vertic Cambisol soil, either densely rooted with Dactylis glomerata (C‐rich) or vegetation‐free (C‐poor). Destructive sampling occurred on days 1, 4 and 14. Microbial biomass (MBC, MBN and MBP), phospholipid fatty acids, DNA and enzymatic activities (acid phosphatase, β‐glucosidase) were analysed to assess microbial responses. Results DNA content was twice as high in C‐rich rooted as in C‐poor bulk soil. In C‐poor soil, urine strongly reduced DNA‐to‐MBC (−166%, day 14) and MBP‐to‐MBC (−23%, day 14), while increased MBN‐to‐MBC (+23% day 14). After 14 days of urine addition, phosphatase‐to‐β‐glucosidase ratios increased from 0.76 to 1.1 in C‐rich but declined in C‐poor soil. In C‐poor bulk soil, urine shaped the microbial community, whereas in C‐rich soil, root exudates dominated. Abundance of bacterial fatty acids increased from 2% to 22% over 14 days. Conclusions In C‐rich soil, urine stimulated microbial growth through C and nutrients availability from both roots and urine, thereby shifting enzymatic activity towards P mining. In contrast, microbial communities in C‐poor soil exhibited restrained growth and stable stoichiometric ratios, adapting to low nutrient supply. These findings highlight that microbial responses to urine input varied between rooted and bulk soil, emphasizing their relevance in soil microbial ecology.
Dynamical Response of Viscous Objects to Gravitational Waves
2025-10-08

We study the dynamical response of viscous materials to gravitational waves, in the context of a fully relativistic theory of fluid dynamics. For the first time, we calculate oscillation modes and scattering properties of viscous stars. Viscous stars absorb high-frequency radiation, following a dispersion relation introduced by Press. In the extremely large viscosity regime, stars would become reflectors of waves, but this regime appears to be forbidden by causality bounds. In the context of black hole mimickers, we show how maximally viscous stars on the threshold of stability mimic the absorption of a black hole with the same mass. Our results suggest that rotating viscous stars will amplify incoming radiation.
APOSTEL-R Recommendations for Reporting Retinal Optical Coherence Tomography Studies in Rodents
2025-10-08

The Advised Protocol for OCT Study Terminology and Elements for reporting OCT studies in rodents (APOSTEL-R) originates from an expert consensus. They will provide guidance throughout the experimental process and will contribute to the standardization and quality improvement of preclinical OCT studies.
Multi-messenger and cosmological constraints on dark matter through two-fluid neutron star modeling
2025-10-08

Abstract In this study, we investigate the impact of dark matter (DM) on neutron stars (NSs) using a two-fluid formalism that treats nuclear matter (NM) and DM as gravitationally coupled components. Employing NM equations of state spanning a wide range of stiffness and a self-interacting asymmetric fermionic DM framework, we explore the emergence of DM core- and halo-dominated structures and their observational implications. Constraints from gravitational waves (GW170817), NICER X-ray measurements (PSR J0030+0451), and pulsar mass limits (PSR J0740+6620) delineate a consistent parameter space for DM properties derived from these multi-messenger observations. DM halo-dominated configurations, while consistent with PSR J0740+6620’s mass limits and NICER’s radius measurements for PSR J0030+0451, are ruled out by the tidal deformability bounds inferred from the GW170817 event. Consequently, the combined limits inferred from the observational data of GW170817, PSR J0030+0451, and PSR J0740+6620 support the plausibility of DM core-dominated configurations. Constraints on the DM self-interaction strength from galaxy cluster dynamics further refine the DM parameter space permitted by NS observations. This work bridges multi-messenger astrophysics and cosmology, providing insights into DM interactions and their implications for NS structure, evolution, and observational signatures.
Challenges in the nonlinear evolution of unequal mass binaries in scalar-Gauss-Bonnet gravity
2025-10-08

It has only recently become possible to simulate the full nonlinear dynamics of binary black holes in scalar-Gauss-Bonnet theories of gravity. The simulations remain technically challenging and evolutions of unequal mass binaries in particular have been difficult to follow through the merger. Even when the merger is successful, accurately quantifying the physical dephasing, as opposed to contributions from transients in the initial data and gauge adjustments, remains difficult. We show the first full simulations of <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:mn>2</a:mn><a:mo>∶</a:mo><a:mn>1</a:mn></a:mrow></a:math> and <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mrow><c:mn>3</c:mn><c:mo>∶</c:mo><c:mn>1</c:mn></c:mrow></c:math> binaries through merger, and we discuss how specific choices in the setup affect the dephasing observed and our ability to obtain reliable results. In cases with weaker couplings, we match the expected PN value for the dephasing, whereas for larger couplings, eccentricity introduced by the initial data transients can lead to artificial deviations. Our work highlights the need for improvements in the initial data methods used, to ensure reliable waveforms are obtained for data analysis in beyond-GR models.