julilili42/papers huggingface dataset:
MYB68 regulates radial endodermal differentiation and suberin patterning
2025-06-01

Roots are composed of concentric layers that surround the vasculature of plants. Of these, the endodermis stands out, as it contains barriers that facilitate selective uptake. In mature root regions, endodermal cells become coated with suberin, a hydrophobic polymer that seals off the inner root parts. Intriguingly, individual endodermal cells, adjacent to the water-conducting xylem, remain unsuberized. These cells are termed "passage cells," based on the assumption that they can facilitate vasculature access in an otherwise sealed-off area. The existence of passage cells suggests that distinct identities and cell files exist within the endodermis that may have overlooked importance. Here, we investigate this in the model plant Arabidopsis thaliana. Our work identifies a genetic regulator of cell-file-specific suberization and passage cell differentiation connected to the xylem. This provides spatiotemporal insights into the mechanism(s) underlying suberization, establishing a framework for the radial organization of the endodermis and highlighting the putative function(s) of passage cells.
Unravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration
2025-06-01

Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment-specific analysis. In this study, we employ a robust RNA-sequencing approach, using microfluidic devices, to generate high-quality axonal transcriptomes from induced pluripotent stem cells-derived cortical neurons (CNs). We achieve high specificity of axonal fractions, ensuring sample purity without contamination. Comparative analysis revealed a unique and specific transcriptional landscape in axonal compartments, characterized by diverse transcript types, including protein-coding mRNAs, RNAs encoding ribosomal proteins, mitochondrial-encoded RNAs and long non-coding RNAs. Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a set of TFs specific to the axon and indicative of their active participation in transcriptional regulation. To investigate transcripts and pathways essential for central motor neuron (MN) degeneration and maintenance we analysed kinesin family member 1C ( KIF1C ) - knockout (KO ) CNs, modelling hereditary spastic paraplegia, a disorder associated with prominent length-dependent degeneration of central MN axons. We found that several key factors crucial for survival and health were absent in KIF1C-KO axons, highlighting a possible role of these also in other neurodegenerative diseases. Taken together, this study underscores the utility of microfluidic devices in studying compartment-specific transcriptomics in human neuronal models and reveals complex molecular dynamics of axonal biology. The impact of KIF1C on the axonal transcriptome not only deepens our understanding of MN diseases but also presents a promising avenue for exploration of compartment-specific disease mechanisms.
Polyunsaturated fatty acid-induced metabolic exhaustion and ferroptosis impair the anti-tumour function of MAIT cells in MASLD
2025-06-01

In this study, we identify a novel immunometabolic axis in which polyunsaturated fatty acids, accumulating in liver tissue in MASLD (metabolic dysfunction-associated steatotic liver disease), drive MAIT (mucosal-associated invariant T) cell dysfunction through lipid peroxide-induced metabolic exhaustion and ferroptosis, ultimately impairing their anti-tumour activity. These findings reveal how MASLD creates an immune-permissive environment that may facilitate hepatocellular carcinoma development and progression and prevent effective immunotherapy. Targeting the polyunsaturated fatty acid-lipid peroxide axis could restore MAIT cell function and enhance current immunotherapeutic anti-cancer strategies.
Rearing Behavior as Indicator of Spatial Novelty and Memory in Developing Rats
2025-06-01

ABSTRACT Among the various forms of exploration, rearing—where rodents stand on their hind legs—reflects the animal's processing of spatial information and response to environmental novelty. Here, we investigated the developmental trajectory of rearing in response to spatial novelty in a standard object–place recognition (OPR) task, with the OPR retrieval phase allowing for a direct comparison of measures of rearing, object exploration, and locomotion as indicators of spatial novelty and memory. Groups of male rats were tested on postnatal day (PD) 25, PD31, PD38, PD48, and at adulthood (PD84). The OPR task comprised a 5‐min encoding phase with the rat exposed to an arena with two identical objects and, 3 h later, a 5‐min retrieval phase in the same arena with one object being displaced to another arena zone. Rearing increased in response to spatial novelty (i.e., the displaced object) at retrieval relative to encoding, with this increase occurring first on PD31, and thus later than preferential object exploration‐based responses emerging already on PD25. Importantly, zone‐specific analyses during retrieval revealed an increase in rearing events in the (now empty) zone where the displaced object is used to be at encoding. This increase was only observed in adult rats (PD84) and likely indicates the presence of specific object–place associations in memory. These findings evidence rearing as behavior covering aspects of spatial novelty complementary to those of object exploration, thereby enabling a more comprehensive characterization of the emergence of spatial episodic memory during early life.
Lipid regulation of adenylyl cyclase Rv1625c from Mycobacterium tuberculosis by its membrane‐domain receptor
2025-06-01

The regulation of mammalian adenylyl cyclases by G‐protein‐coupled receptors and the Gsα subunit of trimeric G‐proteins has been extensively studied, whereas little is known about the regulation of their closely related bacterial cyclases. Here, we focused on the regulation of the adenylyl cyclase Rv1625c from Mycobacterium tuberculosis H37Rv . Rv1625c is a progenitor of mammalian congeners. Exclusively C 18 ‐mono‐unsaturated fatty acids, such as the cis‐ and trans‐isoforms of oleic and vaccenic acids, inhibited the Rv1625c holoenzyme with IC 50 concentrations around 10 μ m . The saturated C 18 fatty acid stearic acid was inactive. A soluble Rv1625c construct, which lacked the membrane domain, was not affected by the mono‐unsaturated C 18 fatty acids, i.e., the inhibition required the presence of the membrane domain, indicating a receptor–ligand interaction. Surprisingly, fatty acid inhibition of Rv1625c was strictly dependent on magnesium ions (Mg 2+ ) as a divalent cation for the substrate adenosine triphosphate (ATP). Although manganese ion (Mn 2+ )–ATP as a substrate greatly increased enzyme activity, Mn 2+ appeared to block intramolecular signal transduction from the membranous receptor domain to the catalytic effector domain. In summary, the results bolster the proposal that adenylyl cyclase regulation by fatty acids is an evolutionarily conserved signaling mode present in bacteria as well as in mammals.
Abiotic Nitrite Incorporation into Organic Matter in Volcanic and Non-Volcanic Soil Within Rainforest Ecosystems
2025-06-01

Understanding nitrogen (N) retention mechanisms in pristine humid temperate rainforest soils is critical for effective ecosystem management and nutrient conservation. The potential abiotic transformation of nitrite (NO2−) into organic N forms in the absence of microbial activity in these ecosystems remains largely unexplored, despite its role in mitigating N leaching. This study focuses on the abiotic incorporation of nitrite (NO2−) into dissolved organic nitrogen (DON) under anoxic conditions, a mechanistic step not directly evaluated in previous research, which employed 15N-labelled nitrate (NO3−). To address this gap, we used 15N-labelled NO2− at 5 and 15 mg L−1 in a lab incubation study under anoxic conditions to trace the contribution of abiotic nitrite transformation to organic N formation in organic matter-rich soils from temperate rainforests developed on both volcanic and non-volcanic parent materials. The added 15N declined rapidly after 15 min by 52% and 60% in both soil solutions, while it started to form labelled DON, increasing by 11% and 34%, after five days of incubation, with the highest accumulation at 15 mg L−1 of 15N-NO2−. These results show that up to 77% of the added 15N-NO2− can be abiotically incorporated into the DON of unpolluted old-growth temperate rainforest, whether developed on volcanic or non-volcanic soils. Nitrogen input has a stronger effect than soil parent material from which the soils originate. This reveals the natural resilience of unpolluted temperate rainforests to N loss, with implications for long-term ecosystem stability and nutrient cycling.
Alpine ice core record of large changes in dust, sea-salt, and biogenic aerosol over Europe during deglaciation
2025-06-01

Abstract Aerosol radiative forcing is an important but often poorly understood component of regional climate. While glacier ice contains the most detailed archives of past atmospheric aerosol composition and temperature, no well-preserved ice records extending into the last climatic transition have been reported for the historically important European region. Here, we use an Alpine ice core to document changes in European aerosols and climate from the end of the last glacial age (LGA) through the Holocene. The core was drilled on a glacier dome in the French Alps called the Dôme du Goûter (DDG), and it provides a stratigraphically intact record of aerosol and climate extending to at least 12 kyears (ky) before present. Although dating near the base of the glacier is not well constrained, the oldest DDG ice layers reflect glacial conditions in western Europe during the LGA. In addition to changes in atmospheric transport, increased sea-salt and dust deposition in western Europe recorded in the LGA ice suggest enhanced westerly winds and more active dust sources, possibly including North Africa. Deposition of terrestrial biogenic indicators during the cold LGA climate was lower, however, consistent with strongly reduced European vegetation. The DDG record of terrestrial biogenic emissions also suggests a decline of European forests throughout the Holocene, resulting from deterioration of climatic conditions and more recently from establishment of the first agricultural societies. The pronounced changes in atmospheric aerosol recorded in Alpine ice imply large variations in aerosol radiative forcing in western Europe during the last 12 ky.
Do Transformers and CNNs Learn Different Concepts of Brain Age?
2025-06-01

ABSTRACT “Predicted brain age” refers to a biomarker of structural brain health derived from machine learning analysis of T1‐weighted brain magnetic resonance (MR) images. A range of machine learning methods have been used to predict brain age, with convolutional neural networks (CNNs) currently yielding state‐of‐the‐art accuracies. Recent advances in deep learning have introduced transformers, which are conceptually distinct from CNNs, and appear to set new benchmarks in various domains of computer vision. Given that transformers are not yet established in brain age prediction, we present three key contributions to this field: First, we examine whether transformers outperform CNNs in predicting brain age. Second, we identify that different deep learning model architectures potentially capture different (sub‐)sets of brain aging effects, reflecting divergent “concepts of brain age”. Third, we analyze whether such differences manifest in practice. To investigate these questions, we adapted a Simple Vision Transformer (sViT) and a shifted window transformer (SwinT) to predict brain age, and compared both models with a ResNet50 on 46,381 T1‐weighted structural MR images from the UK Biobank. We found that SwinT and ResNet performed on par, though SwinT is likely to surpass ResNet in prediction accuracy with additional training data. Furthermore, to assess whether sViT, SwinT, and ResNet capture different concepts of brain age, we systematically analyzed variations in their predictions and clinical utility for indicating deviations in neurological and psychiatric disorders. Reassuringly, we observed no substantial differences in the structure of brain age predictions across the model architectures. Our findings suggest that the choice of deep learning model architecture does not appear to have a confounding effect on brain age studies.
How strong is the rhythm of perception? A registered replication of Hickok et al . (2015)
2025-06-01

Our ability to predict upcoming events is a fundamental component of human cognition. One way in which we do so is by exploiting temporal regularities in sensory signals: the ticking of a clock, falling of footsteps and the motion of waves each provide a structure that may facilitate anticipation. But how strong is the effect of rhythmic anticipation on perception? And to what degree do people vary in their ability to capitalize on these regularities? In 2015, Hickok et al . introduced a behavioural paradigm to assess how a rhythmic auditory stimulus affects perception of subsequent targets (Hickok G, Farahbod H, Saberi K. 2015 The rhythm of perception: entrainment to acoustic rhythms induces subsequent perceptual oscillation. Psychol. Sci. 26 , 1006–1013. (doi: 10.1177/0956797615576533 )). They tested five listeners and found that perception (target detection accuracy) fluctuated rhythmically just like the sound rhythm. Here, we replicate the original finding, assess how likely the finding is to be observed for any individual, and quantify effect size in a large sample of adult listeners ( n = 149). We introduce a model-based analysis approach that allows separate estimates of amplitude and phase information in target detection responses, and quantifies effect size for individual listeners. Together our results strongly support the presence of oscillatory influences on target detection accuracy, as well as substantial variability in the magnitude of this effect across listeners.
Patients’ experiences and usability of a self-directed m-health exercise intervention for knee osteoarthritis: a qualitative study
2025-06-01

Objectives The aim of the study was to analyse patients’ experiences, usability and acceptability of a 12-week self-directed m-health exercise intervention for patients with knee osteoarthritis (OA). Design and participants This qualitative study was included in a randomised controlled trial. After completion of a 12-week m-health exercise intervention, 14 structured telephone interviews were conducted in patients with knee OA. The interviews were audio recorded, transcribed and analysed using a combined deductive and inductive content analysis approach. Setting The study was conducted at a university hospital in southern Germany. Results Four themes were identified: (1) facilitators and (2) barriers for (correct) digital exercise participation, (3) ease of use and (4) outcomes. Participants valued ease of use, comprehensibility, flexibility and certain app features (eg, push notifications as reminders, instruction videos, real-time biofeedback) that facilitated guidance, control and motivation to complete exercises. However, some participants requested some kind of human support. Conclusions The participants demonstrated predominantly positive experiences and acceptability with the self-directed m-health exercise intervention. As some participants lacked human support, we suggest that the optimal treatment option should be selected according to the preferences and needs of the individual patient. Trial registration number DRKS00023269.
Species-specific sensitivity to intracerebroventricular streptozotocin in rats and mice highlights pathways and proteins relevant to Alzheimer’s disease
2025-06-01

Abstract For over three decades, intracerebroventricular streptozotocin (STZ-icv) has been a key non-transgenic rodent model of sporadic Alzheimer’s disease. Traditionally used in rats, its use in mice is growing due to practical advantages. While factors like strain, sex, vehicle, age, and dosage are well studied in STZ-induced diabetes models, their impact on STZ-icv-related cognitive deficits remains poorly understood. To address this gap, we examine species-specific sensitivity to STZ-icv in two widely used rodent strains (Wistar Han rats and C57BL/6 mice) motivated by the finding that, despite reliably inducing cognitive deficits in rats for over 30 years in our lab, the same STZ-icv procedure yields inconsistent results in C57BL/6 mice. To explore this phenomenon, we first constructed a series of allometric models to assess how different STZ-icv concentrations affect predicted exposure in rats and mice. Next, we provide behavioral and immunohistochemical evidence that C57BL/6 mice exhibit resistance to STZ doses that should achieve sufficient neuronal exposure. Finally, we perform an exploratory multiomic analysis, examining differentially expressed proteins in the hippocampus and prefrontal cortex of STZ-icv-treated rats that also show differential expression between Wistar Han rats and C57BL/6 mice, followed by an investigation of these proteins across independent Alzheimer’s disease cohorts. Through this analysis, we identify three understudied proteins—Tagln2, Slc25a3, and Pafah1b3—that may contribute to the differential sensitivity of Wistar Han rats and C57BL/6 mice to STZ-icv and may play a role in the development and progression of Alzheimer’s disease.
SNAr Reactive Pyrazine Derivatives as p53-Y220C Cleft Binders with Diverse Binding Modes
2025-06-01

The promising pyrazine derivatives SN006/7-3, SN006/7-8, and SN006/7-9 were identified, occupying different subsites of the Y220C binding pocket. The compound SN006/7-8 substantially stabilized the thermosensitive cancer mutant Y220C by up to 5.0 °C, representing a strong enhancement over SN006 (1.8 °C) and SN007 (2.0 °C).
Male-dependent resistance to Spiroplasma -induced cytoplasmic incompatibility
2025-06-01

Cytoplasmic incompatibility (CI) caused by bacterial endosymbionts is an embryonic developmental failure between infected host males and uninfected females. Although even closely related hosts can have different CI phenotypes, little is known on the resistance mechanism in non-susceptible hosts. The parasitoid wasp species complex of Lariophagus distinguendus encompasses at least three species, termed clades A, B and C. All three species contain strains infected with the endosymbiotic bacterium Spiroplasma , which causes CI in clade A. We studied the relatedness of Spiroplasma in the species complex, the occurrence of CI in selected strains, and the effect of host strain and sex on CI induction. According to multi-locus sequence typing, all host species carry the same sDis strain. CI was absent in strains of clades B and C. Cross-transferring sDis revealed a male-dependent CI resistance in clade B. Together, this suggests a single infection event in the ancestor of all L. distinguendus clades. Some L. distinguendus strains are susceptible to CI, others are resistant. At least in one strain, resistance to CI is male-dependent, as theory predicts, supporting male-dependent traits as drivers for loss of CI-inducing bacteria. These results facilitate future studies on the mechanism of Spiroplasma -induced CI and its resistance.
Costs of Early Stone Toolmaking cannot Establish the Presence of Know-how Copying
2025-06-01

Abstract Compared to other apes, humans show a distinctive capacity for the cultural learning and transmission of know-how: we extract know-how from other individuals and artifacts in ways that regularly give rise to forms of know-how that no single individual could realistically invent on their own. Such a capacity is plausibly foundational to humans’ striking cultural prowess and hence all that goes with it (e.g., symbolic language, religion). In this article, we critically examine attempts to date the transformation of know-how copying in the hominin lineage through an estimation of the costs of stone toolmaking. More specifically, we take as our target the idea that the costs inherent in making early stone tools, that is, Oldowan and Early Acheulean tools, already likely reflect a meaingful upgrade in hominin know-how copying abilities. Our survey of potentially relevant costs of stone toolmaking is generous, covering: (i) the risks and dangers of toolmaking; (ii) the time, energy, and opportunity costs of toolmaking; and finally (iii) the material costs of toolmaking. Ultimately, we find that, based on current evidence pertaining to these costs, the case for inferring know-how copying abilities in Oldowan or even Early Acheulean stone toolmakers is weak. This skeptical conclusion, combined with independent evidence that the design of stone tools during this period likely remained within the range of what the relevant hominins could invent without know-how copying, points to a later date for the establishment of this crucial human skill.
Linking Virulence and Iron Limitation Response in Staphylococcus aureus: The sRNA IsrR Is Involved in SaeRS Activation
2025-06-02

The Gram-positive opportunistic pathogen <i>Staphylococcus aureus</i> colonizes ∼30% of the human population but also causes various diseases. Precise regulation of genes involved in virulence and metabolic functions is required to adapt to changing host conditions, such as severe restriction of iron availability. In addition to the global regulator Fur (ferric uptake regulator), the iron limitation response of <i>S. aureus</i> is shaped by the recently identified sRNA IsrR (iron sparing response regulator). IsrR mediates an iron sparing response by inhibiting the synthesis of nonessential iron-containing proteins, which are in particular involved in the central metabolism. In addition, we demonstrate that <i>isrR</i> expression is positively associated with α-hemolysin levels and the hemolysis activity of <i>S. aureus</i> HG001. To investigate the influence of IsrR on virulence factor production, we performed a mass spectrometry-based secretome analysis of <i>isrR</i>-expressing and nonexpressing strains under iron-limited and iron-sufficient conditions. The SaeR regulon was positively influenced by the presence of IsrR, and IsrR is likely involved in the activation of the Sae system. Additionally, IsrR also positively affected the protein levels of the <i>isdABCDEFGH</i>-encoded heme uptake system (e.g., IsdB). Taken together, IsrR establishes a link between the iron limitation response and the virulence in <i>S. aureus</i>.
Comment on “Association between quantum paradoxes based on weak values and a realistic interpretation of quantum measurements”
2025-06-02

In their paper [], Aredes and Saldanha analyze several paradoxes related to weak values and present a “general argument” that aims to show that “realistic interpretations <a:math xmlns:a="http://www.w3.org/1998/Math/MathML"><a:mo>...</a:mo></a:math> of weak values lead to inconsistencies.” Although we agree with the identified inconsistencies for the specific weak values analyzed there, in this Comment we demonstrate that the origin of these inconsistencies is not their general argument, which is formally incorrect. We use Bohmian mechanics as a counterexample to confirm that their conclusions are not valid for all weak values and quantum theories. In particular, we show that weak values postselected in position can in fact be interpreted within Bohmian mechanics as properties of quantum systems, detached from any measuring devices, in a consistent and meaningful way.